43 results on '"Sakuno T"'
Search Results
2. Extraction of terminal ileal lipomas to cecum can facilitate endoscopic resection: A case series with video.
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Yamazaki H, Minato Y, Madhu D, Iida T, Banjyoya S, Kimura T, Furuta K, Nagae S, Itou Y, Takeuchi N, Takayanagi S, Kimoto Y, Kano Y, Sakuno T, Ono K, and Ohata K
- Abstract
Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures., Competing Interests: None., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2024
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3. Adjustable length and strength traction by clip with line-pulley securing technique.
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Takayanagi S, Ohata K, Takeuchi N, Kimoto Y, Kano Y, Ono K, Sakuno T, and Minato Y
- Abstract
Competing Interests: The authors disclosed no financial relationships relevant to this publication.
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- 2024
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4. A case of anal canal carcinoma with pagetoid spread that was curatively resected by multiple endoscopic and surgical treatments.
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Furuta K, Kimoto Y, Kano Y, Sakuno T, Ono K, Minato Y, Nakajima K, Miura S, Morikawa T, and Ohata K
- Abstract
A 57-year-old woman with no significant medical history was referred after a colonoscopy for abdominal distension, which revealed a tumor in the lower rectum. Pre-operative colonoscopy showed the tumor was 12 mm in size, located from the anorectal junction to beyond the dentate line, and was diagnosed as high-grade intramucosal neoplasia or shallow submucosal invasive cancer. Endoscopic submucosal dissection was performed, and the lesion was resected en bloc. Pathological examination revealed moderately differentiated tubular adenocarcinoma with tubulovillous adenoma. The stratified squamous epithelium adjacent to the anal side of the lesion showed pagetoid spread of atypical cells with positive horizontal margins. We referred her to a surgeon for radical treatment. The mucosa surrounding the endoscopic submucosal dissection scar was normal on narrow-band imaging magnification. We marked its oral side endoscopically as the resected boundary. Transanal local excision was performed. The horizontal margins were positive because atypical cells had spread into the stratified squamous epithelium of the anorectal side of the lesion. The patient was followed on an outpatient basis. Sixty days postoperatively, residual tumor growth was observed. The second local resection was performed after mapping biopsy. All resection margins were negative, there was no lymphovascular invasion. One year after surgery, no recurrence was observed. Regarding endoscopic findings, there are no reports of endoscopic findings of the rectal mucosa, or the squamous epithelium of the anus of pagetoid spread. Here, we report a review of perianal Paget's Disease that resulted in difficulties in borderline diagnosis of pagetoid spread, resulting in multiple therapeutic interventions., Competing Interests: None., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2024
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5. Endoscopic management of gastric ectopic pancreas with repeated ulcerations and bleeding: A case report.
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Kimura T, Minato Y, Banjoya S, Iida T, Furuta K, Nagae S, Ito Y, Yamazaki H, Takeuchi N, Takayanagi S, Kimoto Y, Kano Y, Sakuno T, Ono K, Miura S, Morikawa T, and Ohata K
- Abstract
A 25-year-old man was referred to our center for investigation of a gastric submucosal tumor and an ulcer that had developed on its oral side. Endoscopic ultrasonography findings suggested the presence of an ectopic pancreas, and treatment with an oral proton pump inhibitor was planned for the ulcer. Over the subsequent 3 years, the patient endured recurring epigastric pain and episodes of passing black stools. Emergency endoscopy revealed that the morphology of the gastric submucosal tumor had transformed into a pedunculated polyp-like morphology with a bleeding ulcer at the apex of the lesion. Endoscopic hemostasis using hemostatic forceps was performed. However, the patient continued to pass black stools. In light of the persistent symptoms and unique morphology of the lesion, endoscopic resection was attempted as a curative approach. The lesion was excised by hot snare polypectomy. Post-treatment, the patient exhibited no signs of recurrence, marking a successful resolution. Three months later, a gastroduodenal endoscopy showed that the excised site had undergone scar formation without recurrence of the lesion. This case holds significant clinical value as it demonstrates the efficacy of a minimally invasive treatment strategy in managing repeated bleeding ulcerations of an ectopic pancreas, ultimately achieving a complete cure., Competing Interests: None., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2024
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6. A case of small bowel aneurysm hemorrhage with submucosal tumor-like findings.
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Banjoya S, Minato Y, Kimoto Y, Kano Y, Sakuno T, Ono K, Osawa M, Horiuchi H, Morikawa T, and Ohata K
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A 51-year-old woman visited our hospital with the chief complaint of tarry stools. Contrast-enhanced abdominal computed tomography revealed leakage of contrast medium into the lumen of the small intestine. Subsequently, a double-balloon endoscopy was performed, which revealed a submucosal mass-like lesion in the jejunum. Although hemostasis was attempted with clips, complete hemostasis was difficult to achieve, and angiographic embolization was performed. Nevertheless, the anemia progressed, and a small bowel resection was performed. Histopathological examination led to a diagnosis of a ruptured submucosal aneurysm of the small intestine. Endoscopic hemostasis is often difficult to achieve for submucosal aneurysms in the intestine. The submucosal tumor-like finding observed on endoscopy in submucosal aneurysms is termed an "SMT-like sign" and is considered an important finding to diagnose aneurysms., Competing Interests: None., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2024
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7. Comparison of cold snare polypectomy for sessile serrated lesions ≥10 mm between experienced and trainee endoscopists: A propensity score matching cohort study.
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Kimoto Y, Sawada R, Banjoya S, Iida T, Kimura T, Furuta K, Nagae S, Ito Y, Yamazaki H, Takeuchi N, Takayanagi S, Kano Y, Sakuno T, Ono K, Negishi R, Sakai E, Minato Y, Chiba H, and Ohata K
- Abstract
Objectives: Previous studies of cold snare polypectomy (CSP) for sessile serrated lesions (SSLs) ≥10 mm were performed by experienced endoscopists, and therefore their skills might have significantly influenced results. In this study, we compared the efficacy and safety of CSP for SSLs ≥10 mm between experienced and trainee endoscopists., Methods: In a 1:1 propensity score matched retrospective cohort study, we compared the complete resection rate, en-bloc resection rate, adverse event rate, and procedure time between experienced and trainee groups. Thirteen endoscopists performed CSP, and we defined the experienced group as endoscopists with board certification from the Japan Gastroenterological Endoscopy Society., Results: We examined 616 lesions with SSLs ≥10 mm resected by CSP between February 2018 and May 2022. We excluded 61 lesions from the analysis because they had simultaneously undergone hot snare polypectomy ( n = 57) or had been taken over by experienced endoscopists from trainees in the CSP procedure ( n = 4). Finally, we identified 217 propensity score-matched pairs ( n = 434). Between experienced and trainee groups, the results were complete resection rate (100 vs. 100%; p = 1.00), en-bloc resection rate (73.2 vs. 75.6%; p = 0.24), adverse event rate (3.2 vs. 2.8%; p = 0.77), or procedure time (6.2 vs. 5.9 min; p = 0.64)., Conclusions: We have demonstrated the safety and efficacy of CSP for SSLs ≥10 mm performed by experienced and trainee endoscopists., Competing Interests: None., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2024
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8. A case of delayed perforation after cold snare polypectomy treated conservatively by endoscopic clip closure.
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Iida T, Minato Y, Banjoya S, Kimura T, Furuta K, Nagae S, Ito Y, Yamazaki H, Takeuchi N, Takayanagi S, Kano Y, Sakuno T, Ono K, and Ohata K
- Abstract
We present the case of a 45-year-old man who underwent a screening total colonoscopy and developed delayed perforation after a cold snare polypectomy in the descending colon and sigmoid colon. The patient developed abdominal pain and was referred to our department for further evaluation and treatment. On clinical examination, we noted lower abdominal tenderness, mild rebound pain, and elevated levels of inflammatory markers. Abdominal contrast-enhanced computed tomography confirmed the presence of free air in the abdomen. Since there were no signs of peritoneal inflammation and the vital signs were stable, we planned to perform endoscopic clip closure of the perforated area. The patient's symptoms improved with conservative management thereafter, including fasting, fluid replacement, and antibiotic administration. The patient was discharged on the 6th hospital day. In this case report, we discuss the usefulness of endoscopic clip closure in managing delayed perforation., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2023
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9. Efficacy and safety of cap-assisted endoscopic mucosal resection for superficial duodenal epithelial neoplasia ≤ 10 mm.
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Kimoto Y, Sawada R, Banjoya S, Iida T, Kimura T, Furuta K, Nagae S, Ito Y, Yamazaki H, Takeuchi N, Takayanagi S, Kano Y, Sakuno T, Ono K, Negishi R, Ohno A, Sakai E, Minato Y, Chiba H, and Ohata K
- Abstract
Background and study aims Endoscopic treatment strategies for small superficial duodenal epithelial neoplasia (SDET) have not been established, and the R0 resection rates of all previously reported endoscopic techniques are somewhat low. Furthermore, no reports of cap-assisted endoscopic mucosal resection (EMRC), which is reportedly associated with a relatively high R0 resection rate, have been evaluated in sufficient numbers of patients. Therefore, we assessed the efficacy and safety of EMRC for SDETs ≤ 10 mm in a retrospective cohort study. Patients and methods We examined a prospectively maintained database and identified 248 consecutive patients (248 lesions) who had undergone endoscopic resection for SDETs ≤ 10 mm between January 2017 and June 2022. Our treatment strategy was consistent, with EMRC indicated for all SDETs ≤ 10 mm without non-lifting signs. The primary endpoint was the R0 resection rate. Results Overall, 20 lesions had non-lifting signs and were selected for endoscopic submucosal dissection, while the remaining 228 lesions were treated with EMRC. As a result of EMRC, the median tumor size was 5 mm, and the mean procedure time was 5 minutes. Most of the lesions (89.2%) were located in the descending part. The R0 resection rate was 97.4% (222/228 cases), and the en bloc resection rate was 99.6%. Only seven patients(3.1%) experienced adverse events (6 patients, delayed bleeding; 1 patient, acute pancreatitis), which were successfully managed without surgical intervention. Furthermore, no recurrences were observed. Conclusions We have demonstrated that EMRC is an effective and safe treatment for SDETs ≤ 10 mm that do not have non-lifting signs., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)
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- 2023
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10. Perigastric abscess caused by delayed perforation after gastric endoscopic submucosal dissection: successful conservative treatment without perforation closure: a case report.
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Nagae S, Kimoto Y, Sawada R, Furuta K, Ito Y, Takeuchi N, Takayanagi S, Kano Y, Ishii R, Sakuno T, Negishi R, Ono K, Minato Y, Muramoto T, and Ohata K
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- Male, Humans, Abscess etiology, Abscess therapy, Conservative Treatment, Ulcer, Stomach, Endoscopy, Gastrointestinal, Treatment Outcome, Endoscopic Mucosal Resection adverse effects, Stomach Neoplasms surgery
- Abstract
Background: Perigastric abscess caused by delayed perforation after endoscopic submucosal dissection is a very rare complication. In principle, delayed perforation after endoscopic submucosal dissection is treated surgically. Herein, we report a case of perigastric abscess caused by delayed perforation after gastric endoscopic submucosal dissection that was treated conservatively, without perforation closure, and in which the patient was discharged from hospital in a short period., Case Presentation: A-74-year-old Asian man was diagnosed with having early gastric cancer on follow-up endoscopy and was admitted to our hospital for endoscopic resection. Endoscopic submucosal dissection was performed without intraoperative complications. On postoperative day 2, the patient complained of a slight abdominal pain localized to the epigastric region and a small amount of melena. A computed tomography scan revealed the presence of free air in the peritoneal cavity, and a little fluid collection abutting the dorsal area of the stomach. An endoscopy examination showed a deep ulcer with the accumulation of pus, suggesting a perforation in the post-endoscopic submucosal dissection ulcer. We diagnosed a perigastric abscess, caused by delayed perforation after endoscopic submucosal dissection, and opted for conservative treatment, leaving the perforation site open to allow spontaneous drainage from the abscess into the stomach. A follow-up computed tomography scan revealed an encapsuled and localized perigastric abscess on postoperative day 5, and the disappearance of the free air and the regression of the perigastric abscess on postoperative day 7. A follow-up endoscopy examination on postoperative day 7 showed the closure of the perforation. Finally, surgery was avoided, and the patient was discharged on postoperative day 14, after a relatively short hospital stay., Conclusion: Regarding the treatment of perigastric abscess, caused by delayed perforation after endoscopic submucosal dissection, leaving the perforation site open to allow spontaneous drainage may shorten the conservative treatment period., (© 2023. The Author(s).)
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- 2023
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11. A Novel Scoring System to Improve the Detection Efficiency of Pancreatic Cystic Lesions in the General Population.
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Tanaka H, Matsusaki S, Asakawa H, Tsuruga S, Nose K, Kumazawa H, Sakuno T, Isono Y, Sase T, Okano H, Saito T, Mukai K, and Nishimura A
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- Humans, Middle Aged, Aged, Pancreas pathology, Abdominal Pain epidemiology, Abdominal Pain etiology, Pancreatic Neoplasms, Pancreatic Cyst diagnostic imaging, Pancreatic Cyst epidemiology, Prediabetic State, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms epidemiology
- Abstract
Objective Pancreatic cystic lesions (PCLs) are known risk factors for pancreatic cancer. Therefore, this study explored the predictors identifying PCLs in a general population and developed a scoring system to help more efficiently diagnose these entities during medical checkups. Methods We reviewed 9,369 examinees of abdominal ultrasound (AUS) during medical checkups between January 2013 and November 2019. Predictors of PCLs were identified using a multivariate logistic regression analysis, and we constructed a scoring system based on these predictors. Results PCLs were detected in 118 (1.3%). Age 50-59 years old [odds ratio (OR) 2.52, 95% confidence interval (CI) 1.18-5.35], 60-69 years old (OR 3.91, 95% CI 1.86-8.26), and ≥70 years old (OR 10.5, 95% CI 5.03-21.7) as well as abdominal pain (OR 1.85, 95% CI 1.14-3.00), alcohol consumption (OR 1.72, 95% CI 1.03-2.89), a family history of pancreatic cancer (OR 2.41, 95% CI 1.09-5.34), and pre-diabetes or diabetes (OR 1.78, 95% CI 1.05-3.00) were predictors of PCLs. The following scores were assigned according to regression coefficients: age (50-59 years old, 1 point; 60-69 years old, 1.5 points; ≥70 years old, 2.5 points); abdominal pain, 1 point, alcohol consumption, 1 point; a family history of pancreatic cancer, 1 point; and pre-diabetes, 1 point. The PCL detection rate increased with the total score: 0.2% for total score 0 point, 5.4% for ≥4.0 points. The area under the curve of the scoring system was 0.75 (95% CI 0.70-0.79). Conclusion Our scoring system allows the risk of PCLs to be determined and may help more efficiently diagnose these entities.
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- 2023
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12. Gastric-type duodenal neoplasms with rapid growth: A report of two cases.
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Sawada R, Kimoto Y, Furuta K, Nagae S, Ito Y, Takeuchi N, Takayanagi S, Kano Y, Ishii R, Sakuno T, Negishi R, Ono K, Minato Y, Muramoto T, Hashimoto H, Morikawa T, and Ohata K
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While duodenal neoplasms of the gastric phenotype are uncommon and their natural history is unknown, gastric neoplasms of gastric phenotype reportedly grow rapidly and can invade the submucosa. Several studies suggest that duodenal neoplasms of gastric phenotype might have a high risk of deep invasion and lymph node metastasis. Duodenal neoplasms of gastric phenotype might also have a high biological malignancy and likely require early treatment if detected. Here, we report two cases of intramucosal duodenal carcinoma with a gastric phenotype that grew rapidly but was successfully resected endoscopically., Competing Interests: None., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)
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- 2022
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13. Early gastric mixed neuroendocrine-non-neuroendocrine neoplasms with endoscopic findings of neuroendocrine cell carcinoma components exposed on the mucosal surface: a case report.
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Ito Y, Kimoto Y, Sawada R, Nagae S, Furuta K, Takeuchi N, Takayanagi S, Kano Y, Ishii R, Sakuno T, Ono K, Negishi R, Minato Y, Muramoto T, and Ohata K
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- Female, Humans, Aged, 80 and over, Gastric Mucosa pathology, Neuroendocrine Cells pathology, Endoscopic Mucosal Resection methods, Neuroendocrine Tumors pathology, Stomach Neoplasms pathology, Adenocarcinoma pathology, Carcinoma, Neuroendocrine pathology
- Abstract
Background: Gastric mixed neuroendocrine-non-neuroendocrine neoplasms are rare malignant tumors. The lack of specific findings makes it difficult to diagnose endoscopically. We report the case of early gastric mixed neuroendocrine-non-neuroendocrine neoplasms treated by endoscopic submucosal dissection., Case Presentation: An 81-year-old Japanese female underwent esophagogastroduodenoscopy for screening and was treated with endoscopic submucosal dissection for the diagnosis of early gastric cancer. Histopathologically, the lesion was diagnosed as mixed neuroendocrine-non-neuroendocrine neoplasms (tubular adenocarcinoma 2 60%, endocrine cell carcinoma 40%), pT1b(submucosa (SM) 900 μm), pUL(-), Ly(+), v(-), pHM0, pVM0. After additional surgical resection without adjuvant chemotherapy, she has had no recurrences or metastases for 3 years., Conclusions: Comparing narrow-band imaging magnified endoscopic findings with pathological findings, the depressed area with a lack of surface structure was consistent with the neuroendocrine cell carcinoma component, while narrow-band imaging magnification findings showed non-network vessels. In this case, we examined endoscopic findings of early stage mixed neuroendocrine-non-neuroendocrine neoplasms in detail and compared it with the pathological findings. We believe that these endoscopic findings contribute to the diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasms and can lead to its early detection., (© 2022. The Author(s).)
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- 2022
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14. Rec8 Cohesin-mediated Axis-loop chromatin architecture is required for meiotic recombination.
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Sakuno T, Tashiro S, Tanizawa H, Iwasaki O, Ding DQ, Haraguchi T, Noma KI, and Hiraoka Y
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- Cell Cycle Proteins, Chromatin, Chromosomal Proteins, Non-Histone, Phosphoproteins genetics, Synaptonemal Complex, Cohesins, Meiosis, Schizosaccharomyces cytology, Schizosaccharomyces genetics, Schizosaccharomyces pombe Proteins genetics
- Abstract
During meiotic prophase, cohesin-dependent axial structures are formed in the synaptonemal complex (SC). However, the functional correlation between these structures and cohesion remains elusive. Here, we examined the formation of cohesin-dependent axial structures in the fission yeast Schizosaccharomyces pombe. This organism forms atypical SCs composed of linear elements (LinEs) resembling the lateral elements of SC but lacking the transverse filaments. Hi-C analysis using a highly synchronous population of meiotic S. pombe cells revealed that the axis-loop chromatin structure formed in meiotic prophase was dependent on the Rec8 cohesin complex. In contrast, the Rec8-mediated formation of the axis-loop structure occurred in cells lacking components of LinEs. To dissect the functions of Rec8, we identified a rec8-F204S mutant that lost the ability to assemble the axis-loop structure without losing cohesion of sister chromatids. This mutant showed defects in the formation of the axis-loop structure and LinE assembly and thus exhibited reduced meiotic recombination. Collectively, our results demonstrate that the Rec8-dependent axis-loop structure provides a structural platform essential for LinE assembly, facilitating meiotic recombination of homologous chromosomes, independently of its role in sister chromatid cohesion., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2022
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15. Rec8 Cohesin: A Structural Platform for Shaping the Meiotic Chromosomes.
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Sakuno T and Hiraoka Y
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- Chromatids, Meiosis genetics, Cohesins, Cell Cycle Proteins genetics, Chromosomal Proteins, Non-Histone genetics
- Abstract
Meiosis is critically different from mitosis in that during meiosis, pairing and segregation of homologous chromosomes occur. During meiosis, the morphology of sister chromatids changes drastically, forming a prominent axial structure in the synaptonemal complex. The meiosis-specific cohesin complex plays a central role in the regulation of the processes required for recombination. In particular, the Rec8 subunit of the meiotic cohesin complex, which is conserved in a wide range of eukaryotes, has been analyzed for its function in modulating chromosomal architecture during the pairing and recombination of homologous chromosomes in meiosis. Here, we review the current understanding of Rec8 cohesin as a structural platform for meiotic chromosomes.
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- 2022
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16. Ischemic hepatitis with infectious endocarditis: A case report.
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Okano H, Okado R, Ito H, Asakawa H, Nose K, Tsuruga S, Tochio T, Kumazawa H, Sakuno T, Isono Y, Tanaka H, Matsusaki S, Sase T, Saito T, Mukai K, and Nishimura A
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A 58-year-old woman was admitted to Suzuka General Hospital with fever. She was diagnosed with infectious endocarditis based on the presence of anterior mitral leaflet vegetation on the echocardiography analysis and isolation of Pseudomonas guariconensis by blood culture. During treatment, the hepatic enzymes levels, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) were increased without any abdominal symptoms. Prolonged prothrombin time (PT) and prothrombin time international normalized ratio were observed, and acute hepatic failure was diagnosed. However, the hepatic injury resolved spontaneously with restoration of the PT value after the hepatic enzymes (AST, ALT, LDH and ALP) peaked. Diffusion-weighted imaging of hepatic magnetic resonance imaging showed diffuse high intensity of the entire liver except for part of the left lobe. The hepatic injury was diagnosed as ischemic hepatitis caused by embolization from the vegetation associated with infectious endocarditis. The recovery from hepatic ischemia was thought to be due to hepatic blood supply from extrahepatic collateral blood. After antibiotic treatment, the patient underwent resection of the vegetation on the anterior mitral valve leaflet. Hepatic artery occlusion is rare, but it may cause severe hepatic complications. During follow-up of infectious endocarditis, clinicians should be aware of the potential for whole organ ischemic damage caused by vessel occlusion, as well as hepatic ischemic damage., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Okano et al.)
- Published
- 2021
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17. Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast.
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Hirano Y, Asakawa H, Sakuno T, Haraguchi T, and Hiraoka Y
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- Endoplasmic Reticulum metabolism, Protein Transport, Telomere metabolism, DNA-Binding Proteins metabolism, Heterochromatin metabolism, Membrane Proteins metabolism, Nuclear Envelope metabolism, Nuclear Proteins metabolism, Schizosaccharomyces genetics, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins metabolism
- Abstract
The nuclear envelope (NE) consists of the inner and outer nuclear membranes (INM and ONM), and the nuclear pore complex (NPC), which penetrates the double membrane. ONM continues with the endoplasmic reticulum (ER). INM and NPC can interact with chromatin to regulate the genetic activities of the chromosome. Studies in the fission yeast Schizosaccharomyces pombe have contributed to understanding the molecular mechanisms underlying heterochromatin formation by the RNAi-mediated and histone deacetylase machineries. Recent studies have demonstrated that NE proteins modulate heterochromatin formation and functions through interactions with heterochromatic regions, including the pericentromeric and the sub-telomeric regions. In this review, we first introduce the molecular mechanisms underlying the heterochromatin formation and functions in fission yeast, and then summarize the NE proteins that play a role in anchoring heterochromatic regions and in modulating heterochromatin formation and functions, highlighting roles for a conserved INM protein, Lem2.
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- 2020
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18. Primary Colorectal Follicular Lymphoma Observed by Magnifying Endoscopy, with a Five-year Follow-up.
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Katsurahara M, Umeda Y, Sakuno T, Tsuboi J, Yamada R, Nakamura M, Hamada Y, Inoue H, Tanaka K, Horiki N, and Takei Y
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- Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Treatment Outcome, Biopsy methods, Colonic Neoplasms diagnosis, Colonic Neoplasms therapy, Endoscopy methods, Lymphoma, Follicular diagnosis, Lymphoma, Follicular therapy, Narrow Band Imaging methods
- Abstract
Colorectal involvement is very rare in cases of follicular lymphoma. Colonoscopy of a 69-year-old man revealed an aggregation of multiple whitish nodules in the sigmoid colon. Magnifying endoscopy with narrow-band imaging demonstrated a coiled and elongated microvascular pattern on the surface and crystal violet staining showed a type I pit pattern. A biopsy showed follicular lymphoma (Grade 1), and no other involvement of lymphoma was detected. Following a diagnosis of primary colorectal follicular lymphoma stage I (Lugano classification), the patient was monitored by watch-and-wait therapy. We documented the endoscopic images of colorectal follicular lymphoma in the present case.
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- 2020
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19. Human Ebp1 rescues the synthetic lethal growth of fission yeast cells lacking Cdb4 and Nup184.
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Osemwenkhae OP, Sakuno T, Hirano Y, Asakawa H, Hayashi-Takanaka Y, Haraguchi T, and Hiraoka Y
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- Adaptor Proteins, Signal Transducing genetics, DNA-Binding Proteins deficiency, HeLa Cells, Humans, RNA-Binding Proteins genetics, Schizosaccharomyces cytology, Synthetic Lethal Mutations, Adaptor Proteins, Signal Transducing metabolism, RNA-Binding Proteins metabolism, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins genetics
- Abstract
Cdb4 is a protein with unknown functions that binds to curved DNA in vitro in the fission yeast Schizosaccharomyces pombe. Homologues of Cdb4 were identified in a wide range of eukaryotes, including human Ebp1. Both S. pombe Cdb4 and human Ebp1 are nonpeptidase members of the methionine aminopeptidase family. It has been reported that Ebp1 homologues are involved in cell growth regulation and differentiation. However, opposing functions have also been considered and debated upon, and the precise biological functions of this conserved protein are largely unknown. S. pombe cdb4 is a nonessential gene, and no obvious phenotypes have been detected in cells with cdb4 gene deletion. In this study, we identified nup184, encoding a component of the nuclear pore complex, as a gene responsible for the synthetic lethal phenotype associated with cdb4. Furthermore, the synthetic lethal phenotype of Cdb4 was suppressed by over-expression of human Ebp1, suggesting that it has conserved crucial functions in S. pombe Cdb4 and human Ebp1. This synthetic lethal phenotype associated with Cdb4 and Nup184 provides a molecular genetics tool to study the functions of S. pombe Cdb4 and its conserved members of proteins, including human Ebp1., (© 2020 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)
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- 2020
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20. Author Correction: Condensin association with histone H2A shapes mitotic chromosomes.
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Tada K, Susumu H, Sakuno T, and Watanabe Y
- Abstract
An Amendment to this Article has been published and is linked from the HTML version of this paper.
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- 2018
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21. Author Correction: Meikin is a conserved regulator of meiosis-I-specific kinetochore function.
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Kim J, Ishiguro KI, Nambu A, Akiyoshi B, Yokobayashi S, Kagami A, Ishiguro T, Pendas AM, Takeda N, Sakakibara Y, Kitajima TS, Tanno Y, Sakuno T, and Watanabe Y
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An Amendment to this Article has been published and is linked from the HTML version of this paper.
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- 2018
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22. Author Correction: Heterochromatin links to centromeric protection by recruiting shugoshin.
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Yamagishi Y, Sakuno T, Shimura M, and Watanabe Y
- Abstract
An Amendment to this Letter has been published and is linked from the HTML version of this paper.
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- 2018
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23. Comparison of endoscopic ultrasound-guided fine-needle aspiration and biopsy with 22-gauge and 25-gauge needles for the "precision medicine" of pancreatic cancer: A retrospective study.
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Yoshizawa N, Yamada R, Sakuno T, Inoue H, Miura H, Takeuchi T, Nakamura M, Hamada Y, Katsurahara M, Tanaka K, Horiki N, and Takei Y
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- Adult, Aged, Data Accuracy, Endoscopic Ultrasound-Guided Fine Needle Aspiration instrumentation, Female, Humans, Immunohistochemistry methods, Male, Middle Aged, Needles statistics & numerical data, Precision Medicine methods, Retrospective Studies, Carcinoma, Pancreatic Ductal pathology, Endoscopic Ultrasound-Guided Fine Needle Aspiration methods, Equilibrative Nucleoside Transporter 1 metabolism, Pancreatic Neoplasms pathology
- Abstract
We compared the sample volume of endoscopic ultrasound-guided fine-needle aspiration and biopsy (EUS-FNAB) specimens obtained by 22-gauge (22G) and 25-gauge (25G) needles, and the accuracy rate.This was a retrospective study in a single tertiary referral center. We investigated 153 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent diagnostic EUS-FNAB before neoadjuvant gemcitabine-based chemoradiotherapy between October 2006 and November 2015. We performed immunohistochemical (IHC) analysis of human equilibrative nucleoside transporter 1 using the remnant cell blocks following pathological PDAC diagnosis. We compared the sampling rate, accuracy rate, and success rate of IHC analysis between 22G and 25G.There were 70 patients in the 22G group and 83 patients in the 25G group. The overall sampling rates on cytology and histology were 100% and 98.0%, respectively. The sampling rate did not differ between the 22G and 25G groups. The overall diagnostic accuracy rates on cytology and histology were 94.8% and 79.7%, respectively. The accuracy rates of 22G and 25G groups on cytology were 94.3% and 95.2%, respectively, whereas those on histology were 80.0% and 79.5%, respectively. The diagnostic accuracy on cytology and histology did not differ significantly between the 22G and 25G groups. Of 153 histology specimens, 69.3% of those with PDAC provided sufficient samples for IHC analysis. The success rate of IHC analysis did not differ significantly between the 22G (67.1%) and 25G (71.1%) groups (P = .60).Both 22G and 25G provided a high diagnostic yield with equivalent accuracy rates on histology. EUS-FNAB specimens obtained using 22G or 25G can be equally adequate for IHC analysis and may be suitable for diagnostic examination. Further investigations such as EUS-FNAB needle design and novel cell block preparation are needed to obtain adequate samples for use in "precision medicine."
- Published
- 2018
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24. Acetylation regulates monopolar attachment at multiple levels during meiosis I in fission yeast.
- Author
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Kagami A, Sakuno T, Yamagishi Y, Ishiguro T, Tsukahara T, Shirahige K, Tanaka K, and Watanabe Y
- Published
- 2017
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25. Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis I.
- Author
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Miyazaki S, Kim J, Yamagishi Y, Ishiguro T, Okada Y, Tanno Y, Sakuno T, and Watanabe Y
- Subjects
- Animals, Cell Adhesion, Cells, Cultured, Centromere genetics, Centromere metabolism, Chromosomal Proteins, Non-Histone metabolism, Chromosomal Proteins, Non-Histone physiology, Kinetochores, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microtubules metabolism, Phosphorylation, Schizosaccharomyces cytology, Schizosaccharomyces growth & development, Spermatocytes cytology, Spermatocytes metabolism, Polo-Like Kinase 1, Cell Cycle Proteins metabolism, Gene Expression Regulation, Fungal, Meiosis, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins metabolism, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins metabolism
- Abstract
In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono-orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1. Consequently, in contrast to the transient kinetochore localization of mitotic Bub1, meiotic Bub1 persists at kinetochores until anaphase I. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization and cohesion protection at centromeres by cooperating with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Furthermore, molecular genetic analyses show a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin that is important for establishing meiosis-specific chromosome segregation. We provide evidence that the meiosis-specific Bub1 regulation is conserved in mouse., (© 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)
- Published
- 2017
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26. Hierarchical Regulation of Centromeric Cohesion Protection by Meikin and Shugoshin during Meiosis I.
- Author
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Miyazaki S, Kim J, Sakuno T, and Watanabe Y
- Abstract
The kinetochore is the key apparatus regulating chromosome segregation. Particularly in meiosis, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation), and sister chromatid cohesion mediated by cohesin is protected at centromeres in the following anaphase. Shugoshin, which localizes to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, Moa1 (meikin), which was initially characterized as a mono-orientation factor in fission yeast, also regulates cohesion protection. Moa1, which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1), inducing the persistent accumulation of Bub1 at kinetochores. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization and cohesion protection at centromeres by cooperating with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Further, molecular genetic analyses reveal a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin during meiosis I., (© 2017 Miyazaki et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2017
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27. Pancreatic Adenocarcinoma Producing Parathyroid Hormone-Related Protein.
- Author
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Yamada R, Tanaka K, Inoue H, Sakuno T, Harada T, Yoshizawa N, Miura H, Takeuchi T, Nakamura M, Katsurahara M, Hamada Y, Horiki N, and Takei Y
- Abstract
A 48-year-old woman presented to our hospital with a 1-year history of a continuous high fever. She was diagnosed with metastatic pancreatic adenocarcinoma accompanied by leukocytosis without infection. Her serum concentration of granulocyte colony-stimulating factor was highly elevated. Forty-five days after initiating chemotherapy, she was readmitted because of a neuropsychiatric disturbance and hypercalcemia. Her serum concentration of parathyroid hormone-related protein (PTH-rP) was elevated. A pretreatment biopsy specimen showed strong cytoplasmic immunoreactivity to anti-PTH-rP antibody, suggesting that overproduction of PTH-rP accounted for the hypercalcemia. Although the patient regained consciousness after treatment, she died of progressive disease 60 days after chemotherapy.
- Published
- 2017
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28. Peripancreatic Tuberculous Lymphadenitis with Biliary Obstruction Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration Biopsy.
- Author
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Yamada R, Inoue H, Yoshizawa N, Kitade T, Tano S, Sakuno T, Harada T, Nakamura M, Katsurahara M, Hamada Y, Tanaka K, Horiki N, and Takei Y
- Subjects
- Common Bile Duct pathology, Constriction, Pathologic, Diagnosis, Differential, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Humans, Male, Middle Aged, Pancreas pathology, Pancreatic Neoplasms diagnosis, Tuberculosis, Lymph Node diagnosis
- Abstract
A 57-year-old man with a history of tuberculosis (TB) was found to have a pancreatic head mass, accompanied by stenosis of the common bile duct. Due to the inherent difficulty in differentiating pancreatic carcinoma from an inflammatory mass, endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) was thus performed. The pathological findings confirmed granuloma with caseous necrosis, and the results of the QuantiFERON TB2G test were positive. Accordingly, the patient was diagnosed with peripancreatic TB and thereafter was successfully treated with anti-TB therapy. Based on the findings of this case, we conclude that EUS-FNAB is a useful modality for the diagnosis of pancreatic TB.
- Published
- 2016
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29. Phosphorylation of cohesin Rec11/SA3 by casein kinase 1 promotes homologous recombination by assembling the meiotic chromosome axis.
- Author
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Sakuno T and Watanabe Y
- Subjects
- Animals, Cell Cycle Proteins genetics, Centromere metabolism, Chromosomal Proteins, Non-Histone genetics, Homologous Recombination physiology, Meiosis genetics, Phosphorylation physiology, Recombination, Genetic genetics, Cohesins, Casein Kinase I metabolism, Cell Cycle Proteins metabolism, Chromosomal Proteins, Non-Histone metabolism, Chromosome Pairing genetics, Chromosome Segregation genetics, Chromosomes, Fungal, Meiosis physiology, Schizosaccharomyces metabolism
- Abstract
In meiosis, cohesin is required for sister chromatid cohesion, as well as meiotic chromosome axis assembly and recombination. However, mechanisms underlying the multifunctional nature of cohesin remain elusive. Here, we show that fission yeast casein kinase 1 (CK1) plays a crucial role in assembling the meiotic chromosome axis (so-called linear element: LinE) and promoting recombination. An in vitro phosphorylation screening assay identified meiotic cohesin subunit Rec11/SA3 as an excellent substrate of CK1. The phosphorylation of Rec11 by CK1 mediates the interaction with the Rec10/Red1/SCP2 axis component, a key step in meiotic chromosome axis assembly, and is dispensable for sister chromatid cohesion. Crucially, the expression of Rec11-Rec10 fusion protein nearly completely bypasses the requirement for CK1 or cohesin phosphorylation for LinE assembly and recombination. This study uncovers a central mechanism of the cohesin-dependent assembly of the meiotic chromosome axis and recombination apparatus that acts independently of sister chromatid cohesion., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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30. Meikin is a conserved regulator of meiosis-I-specific kinetochore function.
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Kim J, Ishiguro K, Nambu A, Akiyoshi B, Yokobayashi S, Kagami A, Ishiguro T, Pendas AM, Takeda N, Sakakibara Y, Kitajima TS, Tanno Y, Sakuno T, and Watanabe Y
- Subjects
- Animals, Cell Cycle Proteins metabolism, Centromere metabolism, Chromosomal Proteins, Non-Histone deficiency, Chromosomal Proteins, Non-Histone genetics, Female, Humans, Infertility genetics, Infertility metabolism, Male, Mice, Molecular Sequence Data, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins metabolism, Saccharomyces cerevisiae Proteins metabolism, Schizosaccharomyces pombe Proteins metabolism, Polo-Like Kinase 1, Chromosomal Proteins, Non-Histone metabolism, Conserved Sequence, Kinetochores metabolism, Meiosis
- Abstract
The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.
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- 2015
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31. Sonographic evaluation of visceral and subcutaneous fat in obese children.
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Sakuno T, Tomita LM, Tomita CM, Giuliano Ide C, Ibagy A, Perin NM, and Poeta LS
- Abstract
Objective: To evaluate sonographic measurements of visceral and subcutaneous fat in children, and to investigate the usefulness of preperitoneal fat (PF) and the abdominal wall fat index (AFI) as parameters to determine visceral fat and presence of nonalcoholic fatty liver disease (NAFLD) in obese children., Materials and Methods: A case-control study of a sample including 44 children (22 cases and 22 controls) matched by sex and age. The Student t test and the Fisher exact test were utilized in the descriptive and bivariate analysis., Results: The sonographic parameters evaluated - subcutaneous cell tissue, PF and intraperitoneal fat, and NAFLD - presented high statistical association with body mass index. NAFLD was observed in eight obese patients (36.36%), and PF and AFI were the variables with highest statistical significance, with p < 0.0001., Conclusion: Ultrasonography is useful tool in the differentiation and quantification of visceral and subcutaneous fat in children. The measures of PF and AFI are useful in the assessment of visceral fat and NAFLD in obese children.
- Published
- 2014
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32. Kinetochore composition and its function: lessons from yeasts.
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Yamagishi Y, Sakuno T, Goto Y, and Watanabe Y
- Subjects
- Centromere metabolism, Kinetochores chemistry, Meiosis physiology, Microtubules metabolism, Mitosis physiology, Protein Transport, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Schizosaccharomyces genetics, Schizosaccharomyces metabolism, Kinetochores metabolism, Saccharomyces cerevisiae physiology, Schizosaccharomyces physiology
- Abstract
Proper chromosome segregation during cell division is essential for proliferation, and this is facilitated by kinetochores, large protein complexes assembled on the centromeric region of the chromosomes. Although the sequences of centromeric DNA differ totally among organisms, many components of the kinetochores assembled on centromeres are very well conserved among eukaryotes. To define the identity of centromeres, centromere protein A (CENP-A), which is homologous to canonical histone H3, acts as a landmark for kinetochore assembly. Kinetochores mediate spindle–microtubule attachment and control the movement of chromosomes during mitosis and meiosis. To conduct faithful chromosome segregation, kinetochore assembly and microtubule attachment are elaborately regulated. Here we review the current understanding of the composition, assembly, functions and regulation of kinetochores revealed mainly through studies on fission and budding yeasts. Moreover, because recent cumulative evidence suggests the importance of the regulation of the orientation of kinetochore–microtubule attachment, which differs distinctly between mitosis and meiosis, we focus especially on the molecular mechanisms underlying this regulation.
- Published
- 2014
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33. Plasticity and epigenetic inheritance of centromere-specific histone H3 (CENP-A)-containing nucleosome positioning in the fission yeast.
- Author
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Yao J, Liu X, Sakuno T, Li W, Xi Y, Aravamudhan P, Joglekar A, Li W, Watanabe Y, and He X
- Subjects
- Autoantigens genetics, Centromere ultrastructure, Centromere Protein A, Chromatin metabolism, Chromosomal Proteins, Non-Histone genetics, Fungal Proteins genetics, Gene Silencing, Genes, Reporter, High-Throughput Nucleotide Sequencing, Histones metabolism, Kinetochores, Models, Genetic, Schizosaccharomyces metabolism, Autoantigens metabolism, Chromosomal Proteins, Non-Histone metabolism, Epigenesis, Genetic, Fungal Proteins metabolism, Gene Expression Regulation, Fungal, Nucleosomes metabolism, Schizosaccharomyces genetics
- Abstract
Nucleosomes containing the specific histone H3 variant CENP-A mark the centromere locus on each chromatin and initiate kinetochore assembly. For the common type of regional centromeres, little is known in molecular detail of centromeric chromatin organization, its propagation through cell division, and how distinct organization patterns may facilitate kinetochore assembly. Here, we show that in the fission yeast S. pombe, a relatively small number of CENP-A/Cnp1 nucleosomes are found within the centromeric core and that their positioning relative to underlying DNA varies among genetically homogenous cells. Consistent with the flexible positioning of Cnp1 nucleosomes, a large portion of the endogenous centromere is dispensable for its essential activity in mediating chromosome segregation. We present biochemical evidence that Cnp1 occupancy directly correlates with silencing of the underlying reporter genes. Furthermore, using a newly developed pedigree analysis assay, we demonstrated the epigenetic inheritance of Cnp1 positioning and quantified the rate of occasional repositioning of Cnp1 nucleosomes throughout cell generations. Together, our results reveal the plasticity and the epigenetically inheritable nature of centromeric chromatin organization.
- Published
- 2013
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34. Bone mass in children and adolescents infected with human immunodeficiency virus.
- Author
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Lima LR, Silva RC, Giuliano Ide C, Sakuno T, Brincas SM, and Carvalho AP
- Subjects
- Absorptiometry, Photon methods, Adolescent, Body Size, CD4-CD8 Ratio, Calcium, Dietary administration & dosage, Case-Control Studies, Chi-Square Distribution, Child, Eating, Exercise, Female, HIV Infections drug therapy, HIV Infections transmission, Humans, Infectious Disease Transmission, Vertical, Male, Sex Distribution, Sex Factors, Socioeconomic Factors, Bone Density physiology, HIV Infections physiopathology, Protease Inhibitors therapeutic use
- Abstract
Objective: To describe bone mineral density (BMD) and bone mineral content (BMC) in children and adolescents infected with the human immunodeficiency virus (HIV), and to compare them with data from the National Health and Nutrition Examination Survey IV (NHANES IV)., Method: The study included 48 children and adolescents (7 to 17 years old) infected with HIV through vertical transmission. BMC and BMD were measured by dual energy absorptiometry X-ray, by calculating z-scores based on data from NHANES IV. The information on clinical and laboratory parameters of infection by HIV was obtained from medical records. Physical activity, calcium intake, and skeletal maturation were also assessed. Descriptive and inferential statistical procedures were used, with levels of significance set at 5%., Results: Seropositive patients presented lower values compared to data from NHANES IV in all z-scores of bone mass (mean=-0.52 to -1.22, SD=0.91 and 0.84, respectively). Based on the subtotal z-BMD, there was a prevalence of 16.7% of children and adolescents with low bone mass for age. Individuals using protease inhibitors presented a lower total z-BMD when compared to the group that did not use (-1.31 vs. -0.79, p=0.02). There were no bone mass differences in relation to physical activity and calcium intake., Conclusions: In the present sample children and adolescents living with HIV have low bone mass for age, and the use of protease inhibitors appears to be related to such decreases., (Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)
- Published
- 2013
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35. Acetylation regulates monopolar attachment at multiple levels during meiosis I in fission yeast.
- Author
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Kagami A, Sakuno T, Yamagishi Y, Ishiguro T, Tsukahara T, Shirahige K, Tanaka K, and Watanabe Y
- Subjects
- Acetylation, DNA Replication, Meiotic Prophase I, Models, Biological, Mutation genetics, Protein Subunits metabolism, Schizosaccharomyces pombe Proteins metabolism, Meiosis, Schizosaccharomyces cytology, Schizosaccharomyces metabolism
- Abstract
In fission yeast, meiotic mono-orientation of sister kinetochores is established by cohesion at the core centromere, which is established by a meiotic cohesin complex and the kinetochore protein Moa1. The cohesin subunit Psm3 is acetylated by Eso1 and deacetylated by Clr6. We show that in meiosis, Eso1 is required for establishing core centromere cohesion during S phase, whereas Moa1 is required for maintaining this cohesion after S phase. The clr6-1 mutation suppresses the mono-orientation defect of moa1Δ cells, although the Clr6 target for this suppression is not Psm3. Thus, several acetylations are crucial for establishing and maintaining core centromere cohesion.
- Published
- 2011
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36. Repositioning of aurora B promoted by chiasmata ensures sister chromatid mono-orientation in meiosis I.
- Author
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Sakuno T, Tanaka K, Hauf S, and Watanabe Y
- Subjects
- Aurora Kinases, Kinetochores enzymology, Protein Serine-Threonine Kinases genetics, Schizosaccharomyces genetics, Schizosaccharomyces pombe Proteins genetics, Chromosome Segregation, Meiosis, Protein Serine-Threonine Kinases metabolism, Schizosaccharomyces enzymology, Schizosaccharomyces pombe Proteins metabolism, Sister Chromatid Exchange
- Abstract
During meiosis I, kinetochores of sister chromatids are juxtaposed or fused and mono-orient, while homologous chromosomes that are paired by chiasmata (bivalents) have to biorient. In the absence of chiasmata, biorientation of sister chromatids (univalents), which carries a risk of aneuploidy, has been occasionally detected in several species, including humans. We show in fission yeast that biorientation of fused sister kinetochores predominates during early prometaphase I. Without chiasmata, this undesirable biorientation of univalents persists and eventually evades the spindle assembly checkpoint, provoking abnormal anaphase. When univalents are connected by chiasmata or by an artificial tether, this erroneous attachment is converted to monopolar attachment and stabilized. This stabilization is apparently achieved by a chromosome configuration that brings kinetochores to the outer edge of the bivalent, while bringing Aurora B, a destabilizer of kinetochore-microtubule attachment, inward. Our results elucidate how chiasmata favor biorientation of bivalents over that of univalents at meiosis I., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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37. Condensin association with histone H2A shapes mitotic chromosomes.
- Author
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Tada K, Susumu H, Sakuno T, and Watanabe Y
- Subjects
- Aurora Kinase B, Aurora Kinases, Binding Sites, Cell Cycle Proteins metabolism, Chromatin metabolism, Chromosomal Proteins, Non-Histone metabolism, HeLa Cells, Humans, Kinetochores metabolism, Microtubules metabolism, Nuclear Proteins metabolism, Phosphorylation, Protein Binding, Protein Serine-Threonine Kinases metabolism, Protein Transport, Schizosaccharomyces cytology, Schizosaccharomyces pombe Proteins metabolism, cdc25 Phosphatases genetics, cdc25 Phosphatases metabolism, Adenosine Triphosphatases metabolism, Chromosomes, Fungal metabolism, DNA-Binding Proteins metabolism, Histones metabolism, Mitosis, Multiprotein Complexes metabolism, Schizosaccharomyces metabolism
- Abstract
Chromosome structure is dynamically regulated during cell division, and this regulation is dependent, in part, on condensin. The localization of condensin at chromosome arms is crucial for chromosome partitioning during anaphase. Condensin is also enriched at kinetochores but its precise role and loading machinery remain unclear. Here we show that fission yeast (Schizosaccharomyces pombe) kinetochore proteins Pcs1 and Mde4--homologues of budding yeast (Saccharomyces cerevisiae) monopolin subunits and known to prevent merotelic kinetochore orientation--act as a condensin 'recruiter' at kinetochores, and that condensin itself may act to clamp microtubule binding sites during metaphase. In addition to the regional recruitment factors, overall condensin association with chromatin is governed by the chromosomal passenger kinase Aurora B. Aurora-B-dependent phosphorylation of condensin promotes its association with histone H2A and H2A.Z, which we identify as conserved chromatin 'receptors' of condensin. Condensin phosphorylation and its deposition onto chromosome arms reach a peak during anaphase, when Aurora B kinase relocates from centromeres to the spindle midzone, where the separating chromosome arms are positioned. Our results elucidate the molecular basis for the spatiotemporal regulation of mitotic chromosome architecture, which is crucial for chromosome partitioning.
- Published
- 2011
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38. Kinetochore geometry defined by cohesion within the centromere.
- Author
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Sakuno T, Tada K, and Watanabe Y
- Subjects
- Centromere genetics, Chromosome Segregation, Meiosis, Microtubules metabolism, Mitosis, Models, Biological, Centromere metabolism, Kinetochores metabolism, Schizosaccharomyces cytology
- Abstract
During cell division microtubules capture chromosomes by binding to the kinetochore assembled in the centromeric region of chromosomes. In mitosis sister chromatids are captured by microtubules emanating from both spindle poles, a process called bipolar attachment, whereas in meiosis I sisters are attached to microtubules originating from one spindle pole, called monopolar attachment. For determining chromosome orientation, kinetochore geometry or structure might be an important target of regulation. However, the molecular basis of this regulation has remained elusive. Here we show the link between kinetochore orientation and cohesion within the centromere in fission yeast Schizosaccharomyces pombe by strategies developed to visualize the concealed cohesion within the centromere, and to introduce artificial tethers that can influence kinetochore geometry. Our data imply that cohesion at the core centromere induces the mono-orientation of kinetochores whereas cohesion at the peri-centromeric region promotes bi-orientation. Our study may reveal a general mechanism for the geometric regulation of kinetochores, which collaborates with previously defined tension-dependent reorientation machinery.
- Published
- 2009
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39. Studies of meiosis disclose distinct roles of cohesion in the core centromere and pericentromeric regions.
- Author
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Sakuno T and Watanabe Y
- Subjects
- Animals, Cell Cycle Proteins physiology, Centromere ultrastructure, Chromatids physiology, Chromatids ultrastructure, Chromosomal Proteins, Non-Histone physiology, Chromosomes ultrastructure, Chromosomes, Fungal physiology, Chromosomes, Fungal ultrastructure, Endopeptidases physiology, Humans, Kinetochores physiology, Kinetochores ultrastructure, Mitosis physiology, Models, Genetic, Plant Proteins genetics, Plant Proteins physiology, Plants genetics, Protein Phosphatase 2 physiology, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae physiology, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins physiology, Schizosaccharomyces genetics, Schizosaccharomyces physiology, Schizosaccharomyces pombe Proteins genetics, Schizosaccharomyces pombe Proteins physiology, Separase, Vertebrates, Cohesins, Centromere physiology, Chromosome Segregation physiology, Chromosomes physiology, Meiosis physiology
- Abstract
During meiosis, a single round of genome duplication is followed by two sequential rounds of chromosome segregation. Through this process, a diploid parent cell generates gametes with a haploid set of chromosomes. A characteristic of meiotic chromosome segregation is a stepwise loss of sister chromatid cohesion along chromosomal arms and at centromeres. Whereas arm cohesion plays an important role in ensuring homologue disjunction at meiosis I, persisting cohesion at pericentromeric regions throughout meiosis I is essential for the faithful equational segregation of sisters in the following meiosis II, similar to mitosis. A widely conserved pericentromeric protein called shugoshin, which associates with protein phosphatase 2A (PP2A), plays a critical role in this protection of cohesin. Another key aspect of meiosis I is the establishment of monopolar attachment of sister kinetochores to spindle microtubules. Cohesion or physical linkage at the core centromeres, where kinetochores assemble, may conjoin sister kinetochores, leading to monopolar attachment. A meiosis-specific kinetochore factor such as fission yeast Moa1 or budding yeast monopolin contributes to this regulation. We propose that cohesion at the core centromere and pericentromeric regions plays distinct roles, especially in defining the orientation of kinetochores.
- Published
- 2009
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40. Heterochromatin links to centromeric protection by recruiting shugoshin.
- Author
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Yamagishi Y, Sakuno T, Shimura M, and Watanabe Y
- Subjects
- Chromobox Protein Homolog 5, Chromosome Segregation, Humans, Meiosis, Mitosis, Protein Binding, Protein Transport, Schizosaccharomyces genetics, Schizosaccharomyces metabolism, Cohesins, Cell Cycle Proteins metabolism, Centromere metabolism, Chromosomal Proteins, Non-Histone metabolism, Heterochromatin metabolism, Schizosaccharomyces pombe Proteins metabolism
- Abstract
The centromere of a chromosome is composed mainly of two domains, a kinetochore assembling core centromere and peri-centromeric heterochromatin regions. The crucial role of centromeric heterochromatin is still unknown, because even in simpler unicellular organisms such as the fission yeast Schizosaccharomyces pombe, the heterochromatin protein Swi6 (HP1 homologue) has several functions at centromeres, including silencing gene expression and recombination, enriching cohesin, promoting kinetochore assembly, and, ultimately, preventing erroneous microtubule attachment to the kinetochores. Here we show that the requirement of heterochromatin for mitotic chromosome segregation is largely replaced by forcibly enriching cohesin at centromeres in fission yeast. However, this enrichment of cohesin is not sufficient to replace the meiotic requirement for heterochromatin. We find that the heterochromatin protein Swi6 associates directly with meiosis-specific shugoshin Sgo1, a protector of cohesin at centromeres. A point mutation of Sgo1 (V242E), which abolishes the interaction with Swi6, impairs the centromeric localization and function of Sgo1. The forced centromeric localization of Sgo1 restores proper meiotic chromosome segregation in swi6 cells. We also show that the direct link between HP1 and shugoshin is conserved in human cells. Taken together, our findings suggest that the recruitment of shugoshin is the important primary role for centromeric heterochromatin in ensuring eukaryotic chromosome segregation.
- Published
- 2008
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41. Upf1 potentially serves as a RING-related E3 ubiquitin ligase via its association with Upf3 in yeast.
- Author
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Takahashi S, Araki Y, Ohya Y, Sakuno T, Hoshino S, Kontani K, Nishina H, and Katada T
- Subjects
- Amino Acid Sequence, Codon, Nonsense metabolism, Molecular Sequence Data, RNA Helicases genetics, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Signal Transduction, Ubiquitin-Protein Ligases genetics, RING Finger Domains, RNA Helicases metabolism, RNA Stability, RNA-Binding Proteins metabolism, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae Proteins metabolism, Ubiquitin-Protein Ligases metabolism
- Abstract
Three Upf proteins are essential to the nonsense-mediated mRNA decay (NMD) pathway. Although these proteins assemble on polysomes for recognition of aberrant mRNAs containing premature termination codons, the significance of this assembly remains to be elucidated. The Cys- and His-rich repeated N terminus (CH domain) of Upf1 has been implicated in its binding to Upf2. Here, we show that CH domain also plays a RING-related role for Upf1 to exhibit E3 ubiquitin ligase activity in yeast. Despite the sequence divergence from typical E3-RING fingers, the CH domain of yeast Upf1 specifically and directly interacted with the yeast E2 Ubc3. Interestingly, Upf1 served as a substrate for the in vitro self-ubiquitination, and the modification required its association with Upf3 rather than Upf2. Substitution of the coordinated Cys and His residues in the CH domain impaired not only self-ubiquitination of Upf1 but also rapid decay of aberrant mRNAs. These results suggest that Upf1 may serve as an E3 ubiquitin ligase upon its association with Upf3 and play an important role in signaling to the NMD pathway.
- Published
- 2008
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42. Shugoshin collaborates with protein phosphatase 2A to protect cohesin.
- Author
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Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, and Watanabe Y
- Subjects
- Cell Cycle Proteins genetics, HeLa Cells, Humans, Meiosis, Mitosis, Multiprotein Complexes genetics, Multiprotein Complexes metabolism, Phosphoprotein Phosphatases classification, Phosphoprotein Phosphatases genetics, Phosphoproteins metabolism, Phosphorylation, Protein Binding, Protein Phosphatase 2, Schizosaccharomyces cytology, Schizosaccharomyces genetics, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins metabolism, Cohesins, Cell Cycle Proteins metabolism, Centromere metabolism, Chromatids metabolism, Chromosomal Proteins, Non-Histone metabolism, Chromosome Pairing, Nuclear Proteins metabolism, Phosphoprotein Phosphatases metabolism
- Abstract
Sister chromatid cohesion, mediated by a complex called cohesin, is crucial--particularly at centromeres--for proper chromosome segregation in mitosis and meiosis. In animal mitotic cells, phosphorylation of cohesin promotes its dissociation from chromosomes, but centromeric cohesin is protected by shugoshin until kinetochores are properly captured by the spindle microtubules. However, the mechanism of shugoshin-dependent protection of cohesin is unknown. Here we find a specific subtype of serine/threonine protein phosphatase 2A (PP2A) associating with human shugoshin. PP2A colocalizes with shugoshin at centromeres and is required for centromeric protection. Purified shugoshin complex has an ability to reverse the phosphorylation of cohesin in vitro, suggesting that dephosphorylation of cohesin is the mechanism of protection at centromeres. Meiotic shugoshin of fission yeast also associates with PP2A, with both proteins collaboratively protecting Rec8-containing cohesin at centromeres. Thus, we have revealed a conserved mechanism of centromeric protection of eukaryotic chromosomes in mitosis and meiosis.
- Published
- 2006
- Full Text
- View/download PDF
43. Interaction between Ski7p and Upf1p is required for nonsense-mediated 3'-to-5' mRNA decay in yeast.
- Author
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Takahashi S, Araki Y, Sakuno T, and Katada T
- Subjects
- Adaptor Proteins, Signal Transducing, Base Sequence, Cytoplasm metabolism, Hydrolysis, Molecular Sequence Data, Oligodeoxyribonucleotides, Plasmids, Precipitin Tests, Protein Binding, RNA, Messenger genetics, GTP-Binding Proteins metabolism, RNA Helicases metabolism, RNA, Messenger metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins metabolism
- Abstract
Aberrant mRNAs containing premature termination codons (PTC-mRNAs) are degraded by a conserved surveillance system, referred to as the nonsense- mediated decay (NMD) pathway. Although NMD is reported to operate on the decapping and 5'-to-3' exonucleolytic decay of PTC-mRNAs without affecting deadenylation, a role for an opposite 3'-to-5' decay pathway remains largely unexplored. In this study, we have characterized the 3'-to-5' directed mRNA degradation in the yeast NMD pathway. PTC-mRNAs are stabilized in yeast cells lacking the components of 3'-to-5' mRNA-decay machinery. The 3'-to-5' directed degradation of PTC-mRNAs proceeds more rapidly than that of the PTC-free transcript, in a manner dependent on the cytoplasmic exosome and Upf proteins. Moreover, Upf1p, but not Upf2p, interacts physically with an N-terminal domain of Ski7p, although the interaction requires Upf2p. The efficiency of 3'-to-5' directed degradation of PTC-mRNAs is impaired by overexpression of Ski7p N-domain fragments that contain a sequence of the Upf1p-interaction region. These data suggest that the activation of 3'-to-5' directed NMD is mediated through the interaction between Upf1p and the Ski7p N domain.
- Published
- 2003
- Full Text
- View/download PDF
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