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Start Over Descriptor "14/32" Journal nature communications
4 results on '"14/32"'

1. FANCM promotes class I interfering crossovers and suppresses class II non-interfering crossovers in wheat meiosis

Author

Stuart D. Desjardins, James Simmonds, Inna Guterman, Kostya Kanyuka, Amanda J. Burridge, Andrew J. Tock, Eugenio Sanchez-Moran, F. Chris H. Franklin, Ian R. Henderson, Keith J. Edwards, Cristobal Uauy, James D. Higgins, Simmonds, James [0000-0003-4936-1694], Kanyuka, Kostya [0000-0001-6324-4123], Burridge, Amanda J [0000-0002-0140-5523], Tock, Andrew J [0000-0002-6590-8314], Henderson, Ian R [0000-0001-5066-1489], Uauy, Cristobal [0000-0002-9814-1770], Higgins, James D [0000-0001-6027-8678], Apollo - University of Cambridge Repository, Tock, Andrew [0000-0002-6590-8314], and Henderson, Ian [0000-0001-5066-1489]

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Multidisciplinary, 45, 631/80/641/1633, article, food and beverages, nutritional and metabolic diseases, 631/208/1405, 45/77, General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology, 14/32, Meiosis, Plant Breeding, hemic and lymphatic diseases, 631/449/2491, 14/63, Crossing Over, Genetic, Triticum
Abstract

FANCM suppresses crossovers in plants by unwinding recombination intermediates. In wheat, crossovers are skewed toward the chromosome ends, thus limiting generation of novel allelic combinations. Here, we observe that FANCM maintains the obligate crossover in tetraploid and hexaploid wheat, thus ensuring that every chromosome pair exhibits at least one crossover, by localizing class I crossover protein HEI10 at pachytene. FANCM also suppresses class II crossovers that increased 2.6-fold in fancm msh5 quadruple mutants. These data are consistent with a role for FANCM in second-end capture of class I designated crossover sites, whilst FANCM is also required to promote formation of non-crossovers. In hexaploid wheat, genetic mapping reveals that crossovers increase by 31% in fancm compared to wild type, indicating that fancm could be an effective tool to accelerate breeding. Crossover rate differences in fancm correlate with wild type crossover distributions, suggesting that chromatin may influence the recombination landscape in similar ways in both wild type and fancm.

Published
2022
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2. Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture

Author

Hidewaki Nakagawa, Hiroshi Aikata, Mónica Martínez-Fernández, Atsushi Ono, Marta Tojo, Peter J. Campbell, Adrian Baez-Ortega, Kerstin Haase, Jonas Demeulemeester, Adam Butler, Xavier Forns, Rosanna Abal, Keiran Raine, Javier Temes, Urtzi Garaigorta, Daniel García-Souto, Carmen Rivas, Aitor Rodriguez-Casanova, Eva G. Alvarez, Sonia Zumalave, Jorge Zamora, Hiroki Yamaue, Clemency Jolly, Yang Li, Peter Van Loo, Jose M. C. Tubio, Kazuaki Chayama, Iago Otero, Sofía Pérez-del-Pulgar, Masaki Ueno, Miguel Blanco, Shinya Hayami, Sandra Rodriguez-Perales, Kazuhiro Maejima, Jorge Rodríguez-Castro, Angel Diaz-Lagares, Raúl Torres-Ruiz, Ana Pequeño-Valtierra, Juan Ruiz-Bañobre, Ana Oitaben, Bernardo Rodriguez-Martin, Paula Otero, Alicia L. Bruzos, Álvarez, Eva G [0000-0002-3522-5088], Demeulemeester, Jonas [0000-0002-2660-2478], Otero, Paula [0000-0001-5614-1468], García-Souto, Daniel [0000-0002-0997-8799], Temes, Javier [0000-0003-3370-4728], Rodriguez-Martin, Bernardo [0000-0003-4693-3140], Oitaben, Ana [0000-0002-4877-6145], Bruzos, Alicia L [0000-0003-4362-545X], Haase, Kerstin [0000-0002-0944-5618], Zumalave, Sonia [0000-0002-2108-1861], Rodríguez-Castro, Jorge [0000-0003-2912-9601], Rodriguez-Casanova, Aitor [0000-0002-9828-3613], Raine, Keiran M [0000-0002-5634-1539], Otero, Iago [0000-0002-7924-693X], Blanco, Miguel G [0000-0002-2883-7326], Ruiz-Bañobre, Juan [0000-0003-0755-4295], Pérez-Del-Pulgar, Sofía [0000-0002-9890-300X], Torres-Ruiz, Raúl [0000-0001-9606-0398], Rodriguez-Perales, Sandra [0000-0001-7221-3636], Garaigorta, Urtzi [0000-0002-0683-5725], Campbell, Peter J [0000-0002-3921-0510], Van Loo, Peter [0000-0003-0292-1949], Tubio, Jose MC [0000-0003-3540-2459], and Apollo - University of Cambridge Repository

Subjects
LIVER, Hepatocellular carcinoma, General Physics and Astronomy, medicine.disease_cause, Genome, 631/67/1858, Ecology,Evolution & Ethology, Cancer genomics, Tumour virus infections, 631/208/69, Human Biology & Physiology, Multidisciplinary, Liver Neoplasms, ASSOCIATION, READ ALIGNMENT, TRANSLOCATION, Multidisciplinary Sciences, Gene Expression Regulation, Neoplastic, Science & Technology - Other Topics, Liver cancer, Genetics & Genomics, Hepatitis B virus, Carcinoma, Hepatocellular, Science, Virus Integration, 631/67/1504/1610/4029, 45/23, Biology, General Biochemistry, Genetics and Molecular Biology, Virus, Article, 14/32, CHROMOSOMES, medicine, Humans, Gene, Computational & Systems Biology, Science & Technology, Whole Genome Sequencing, MUTATIONS, Genome, Human, Cancer, General Chemistry, Tumour Biology, medicine.disease, digestive system diseases, DNA, Viral, Cancer research, Carcinogenesis
Abstract

Most cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. Here, using multiplatform sequencing technologies, we identify and characterize a remarkable mutational mechanism in human hepatocellular carcinoma caused by Hepatitis B virus, by which DNA molecules from the virus are inserted into the tumour genome causing dramatic changes in its configuration, including non-homologous chromosomal fusions, dicentric chromosomes and megabase-size telomeric deletions. This aberrant mutational mechanism, present in at least 8% of all HCC tumours, can provide the driver rearrangements that a cancer clone requires to survive and grow, including loss of relevant tumour suppressor genes. Most of these events are clonal and occur early during liver cancer evolution. Real-time timing estimation reveals some HBV-mediated rearrangements occur as early as two decades before cancer diagnosis. Overall, these data underscore the importance of characterising liver cancer genomes for patterns of HBV integration., Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient samples to study the timing and alterations induced by HBV insertions.

Published
2021

3. WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling

Author

Cristina Beltrami, Owen J. L. Rackham, Costanza Emanueli, Nithya Devapragash, Wei-Ping Yu, Xi-Ming Sun, Stuart A. Cook, Norbert Hubner, Francesco Pesce, Ee Ling Heng, Elisabeth Tan, Aida Moreno-Moral, Enrique Lara-Pezzi, Gianni D Angelini, Enrico Petretto, Huimei Chen, Paul J.R. Barton, Nathan Harmston, Michal Pravenec, Sebastian Schafer, Maxime Rotival, Nicole Tee, Massimilano Mancini, Leanne E. Felkin, Leonardo Bottolo, Prashant K. Srivastava, Kirill Shkura, Cardiovascular and Metabolic Disorders [Singapor] (cvmd), Duke-NUS Medical School [Singapore], Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Ospedale San Giovanni di Dio, Firenze, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Faculty of Medicine [London, UK], Imperial College London, Agency for science, technology and research [Singapore] (A*STAR), Institute of Molecular and Cell Biology, National University of Singapore (NUS)-Agency for science, technology and research [Singapore] (A*STAR), MRC London Institute of Medical Sciences (LMC), National Heart Centre Singapore (NHCS), Royal Brompton and Harefield NHS Foundation Trust, Cardiovascular Research Centre [London], Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), University of Bristol [Bristol], Institute of Physiology [Prague], Czech Academy of Sciences [Prague] (CAS), University of Cambridge [UK] (CAM), The Alan Turing Institute, MRC Biostatistics Unit [Cambridge, UK], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], The research was primarily supported by National Medical Research Council (NMRC) Singapore grant NMRC/CBRG/0106/2016 (to E.P.) and the British Heart Foundation (BHF) Ph.D. Studentship grant FS/11/25/28740 (to E.P). We acknowledge additional funding support from European Union FP7 CardioNeT-ITN-289600 (to E.L.-P., S.A.C., and P.J.R.B.), Heart Research UK (to P.J.R.B.), NIHR CV BRU of Royal Brompton and Harefield, NHS Foundation Trust (to S.A.C. and P.J.R.B.), BHF (to S.A.C.), Leducq Foundation (to S.A.C.), MRC UK (to S.A.C.), BHF Program Grant no. RG/15/5/31446 (to C.E. and E.P.). M.P. was supported by Praemium Academiae award of the Czech Academy of Sciences and grant 14-36804G from the Czech Science Foundation., We wish to thank Dr. Jacques Behmoaras for contributing critical and constructive comments to the manuscript., European Project: 289600,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,CARDIONET(2012), Moreno-Moral, Aida [0000-0002-8155-3146], Barton, Paul J. R. [0000-0002-1165-7767], Schafer, Sebastian [0000-0002-6909-8275], Bottolo, Leonardo [0000-0002-6381-2327], Cook, Stuart A. [0000-0001-6628-194X], Petretto, Enrico [0000-0003-2163-5921], Apollo - University of Cambridge Repository, National Medical Research Council (Singapur), British Heart Foundation, Unión Europea. Comisión Europea, National Institutes of Health (Estados Unidos), Czech Science Foundation, Fondation Leducq, NHS Foundation Trusth, University of Bari Aldo Moro (UNIBA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Leducq Foundation for Cardiovascular Research, Commission of the European Communities, Heart Research UK, Medical Research Council (MRC), Barton, Paul JR [0000-0002-1165-7767], and Cook, Stuart A [0000-0001-6628-194X]

Subjects
Male, 45/43, BLOOD-PRESSURE, 02 engineering and technology, MESH: Protein Isoforms, MESH: Heart Diseases / genetics, Mice, Transforming Growth Factor beta, 42/44, Fibrosis, Protein Isoforms, Medicine, MESH: Animals, lcsh:Science, MESH: Ubiquitin-Protein Ligases / genetics, MESH: Fibrosis / metabolism, MESH: Genetic Predisposition to Disease* / genetics, GENE-EXPRESSION, Regulation of gene expression, Extracellular Matrix Proteins, MESH: Middle Aged, MESH: Fibrosis / genetics, TGF-BETA, MESH: Heart Diseases / metabolism, MESH: Ubiquitin-Protein Ligases / metabolism, 3. Good health, Cell biology, Ubiquitin ligase, FIBROBLAST, MESH: Young Adult, Science & Technology - Other Topics, 64/60, Cardiomyopathies, 0210 nano-technology, Cardiac function curve, Science, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, REVEALS, Humans, Aged, MESH: Adolescent, Science & Technology, MESH: Humans, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], IDENTIFICATION, MESH: Smad2 Protein / metabolism, MESH: Extracellular Matrix Proteins / metabolism, MESH: Adult, MESH: Cardiomyopathies / metabolism, medicine.disease, 030104 developmental biology, Cardiovascular and Metabolic Diseases, E3 UBIQUITIN LIGASE, RAT, DETERMINANT, lcsh:Q, Myocardial fibrosis, MESH: Female, 0301 basic medicine, Cardiac fibrosis, General Physics and Astronomy, Smad2 Protein, Gene Regulatory Networks, 13/89, MESH: Aged, MESH: Transforming Growth Factor beta / metabolism, Multidisciplinary, biology, MESH: Smad2 Protein / genetics, article, Middle Aged, MESH: Cardiomyopathies / genetics, 021001 nanoscience & nanotechnology, 692/4019/592/75/74, MESH: Gene Expression Regulation, Multidisciplinary Sciences, Centre for Surgical Research, HEART-FAILURE, Female, 38/39, Adult, Adolescent, Heart Diseases, MESH: Mice, Transgenic, Ubiquitin-Protein Ligases, Mice, Transgenic, 14/32, 82/80, Young Adult, Animals, Genetic Predisposition to Disease, 14/35, MESH: Mice, Pressure overload, business.industry, General Chemistry, MESH: Male, Gene Expression Regulation, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Ubiquitin ligases, Heart failure, 13/51, biology.protein, 631/45/474/2073, MESH: Gene Regulatory Networks, business
Abstract

Cardiac fibrosis is a final common pathology in inherited and acquired heart diseases that causes cardiac electrical and pump failure. Here, we use systems genetics to identify a pro-fibrotic gene network in the diseased heart and show that this network is regulated by the E3 ubiquitin ligase WWP2, specifically by the WWP2-N terminal isoform. Importantly, the WWP2-regulated pro-fibrotic gene network is conserved across different cardiac diseases characterized by fibrosis: human and murine dilated cardiomyopathy and repaired tetralogy of Fallot. Transgenic mice lacking the N-terminal region of the WWP2 protein show improved cardiac function and reduced myocardial fibrosis in response to pressure overload or myocardial infarction. In primary cardiac fibroblasts, WWP2 positively regulates the expression of pro-fibrotic markers and extracellular matrix genes. TGFβ1 stimulation promotes nuclear translocation of the WWP2 isoforms containing the N-terminal region and their interaction with SMAD2. WWP2 mediates the TGFβ1-induced nucleocytoplasmic shuttling and transcriptional activity of SMAD2., Pathological cardiac fibrosis is a hallmark of diseases leading to heart failure. Here, the authors used systems genetics to identify a pro-fibrotic gene network regulated by WWP2, a E3 ubiquitin ligase, which orchestrates the nucleocytoplasmic shuttling and transcriptional activity of SMAD2 in the diseased heart.

Published
2019
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4. A high-content RNAi screen reveals multiple roles for long noncoding RNAs in cell division

Author

Fanni Gergely, Jasmin Mangei, John C. Marioni, Patrice Mascalchi, Chris Bakal, Duncan T. Odom, Christina Ernst, Alexis R. Barr, Aisling M. Redmond, Vicky Bousgouni, Lovorka Stojic, Aaron T. L. Lun, Stojic, Lovorka [0000-0001-6691-3396], Lun, Aaron T. L. [0000-0002-3564-4813], Redmond, Aisling M. [0000-0001-9070-1780], Barr, Alexis R. [0000-0002-6684-8114], Bakal, Chris [0000-0002-0413-6744], Odom, Duncan T. [0000-0001-6201-5599], Gergely, Fanni [0000-0002-2441-8095], Apollo - University of Cambridge Repository, Lun, Aaron TL [0000-0002-3564-4813], Redmond, Aisling M [0000-0001-9070-1780], Barr, Alexis R [0000-0002-6684-8114], Odom, Duncan T [0000-0001-6201-5599], and Lun, Aaron T L [0000-0002-3564-4813]

Subjects
0301 basic medicine, binding, Cell division, General Physics and Astronomy, comparative genomics, 13, 14, 631/337/641/1655, Transcriptome, Chromosome segregation, 0302 clinical medicine, RNA interference, lcsh:Science, 0303 health sciences, Multidisciplinary, 030302 biochemistry & molecular biology, High-throughput screening, Cell biology, Multidisciplinary Sciences, spindle-assembly checkpoint, 631/337/384/2568, Science & Technology - Other Topics, RNA Interference, RNA, Long Noncoding, Cell Division, Cell type, Science, Mitosis, gene repression, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 38, 38/91, 14/32, 03 medical and health sciences, Microtubule, expression, 38/89, 631/208/200, Humans, 030304 developmental biology, Science & Technology, microtubule organization, Proteins, General Chemistry, mitotic block, 49, High-Throughput Screening Assays, Gene regulation, 030104 developmental biology, tubulin, 14/63, Long non-coding RNAs, lcsh:Q, tppp/p25, 631/1647/2163, protein, 030217 neurology & neurosurgery, Cytokinesis, HeLa Cells
Abstract

Genome stability relies on proper coordination of mitosis and cytokinesis, where dynamic microtubules capture and faithfully segregate chromosomes into daughter cells. With a high-content RNAi imaging screen targeting more than 2,000 human lncRNAs, we identify numerous lncRNAs involved in key steps of cell division such as chromosome segregation, mitotic duration and cytokinesis. Here, we provide evidence that the chromatin-associated lncRNA, linc00899, leads to robust mitotic delay upon its depletion in multiple cell types. We perform transcriptome analysis of linc00899-depleted cells and identify the neuronal microtubule-binding protein, TPPP/p25, as a target of linc00899. We further show that linc00899 binds TPPP/p25 and suppresses its transcription. In cells depleted of linc00899, upregulation of TPPP/p25 alters microtubule dynamics and delays mitosis. Overall, our comprehensive screen uncovers several lncRNAs involved in genome stability and reveals a lncRNA that controls microtubule behaviour with functional implications beyond cell division., Long noncoding RNAs (lncRNAs) regulate key steps of cell division. Here, the authors perform a comprehensive RNAi imaging screen targeting more than 2,000 human lncRNAs, and suggest a role of chromatin-associated linc00899 in regulation of cell division by suppressing the transcription of microtubule-binding protein TPPP/p25.

Published
2019

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