17 results on '"Cipressa, F."'
Search Results
2. Low dose rate γ-irradiation protects fruit fly chromosomes from double strand breaks and telomere fusions by reducing the esi-RNA biogenesis factor Loquacious
- Author
-
Porrazzo, A., Cipressa, F., De Gregorio, A., De Pittà, C., Sales, G., Ciapponi, L., Morciano, P., Esposito, G., Tabocchini, M. A., and Cenci, G.
- Published
- 2022
- Full Text
- View/download PDF
3. NBS1 interacts with HP1 to ensure genome integrity
- Author
-
Jacopo Albanesi, Laura Ciapponi, Fabio Polticelli, Simona Cugusi, Giovanni Cenci, Valentina Brandi, Francesca Cipressa, Antonio Antoccia, Alessandra di Masi, Maria Lina Moroni, Rosa Pennisi, Giuseppe Bosso, Fioranna Renda, Bosso, G, Cipressa, F, Moroni, Ml, Pennisi, R, Albanesi, J, Brandi, V, Cugusi, S, Renda, F, Ciapponi, L, Polticelli, F, Antoccia, A, di Masi, A, and Cenci, G
- Subjects
Male ,Cancer Research ,Chromosomal Proteins, Non-Histone ,DNA damage ,Genome, Insect ,Immunology ,Diseases ,Cell Cycle Proteins ,Biology ,NBS1 ,Article ,Chromosomes ,Genomic Instability ,NBS1, HP1, Drosophila, genome stability ,Cellular and Molecular Neuroscience ,medicine ,Animals ,Drosophila Proteins ,Humans ,lcsh:QH573-671 ,Nijmegen Breakage Syndrome ,Endodeoxyribonucleases ,lcsh:Cytology ,HP1 ,DNA replication ,Nuclear Proteins ,Cell Biology ,Fibroblasts ,medicine.disease ,Telomere ,Chromatin ,Cell biology ,Drosophila melanogaster ,Exodeoxyribonucleases ,Gene Expression Regulation ,MRN complex ,Chromobox Protein Homolog 5 ,Rad50 ,Mutation ,embryonic structures ,Female ,Drosophila ,Heterochromatin protein 1 ,genome stability ,Nijmegen breakage syndrome ,DNA Damage - Abstract
Heterochromatin Protein 1 (HP1) and the Mre11-Rad50-Nbs1 (MRN) complex are conserved factors that play crucial role in genome stability and integrity. Despite their involvement in overlapping cellular functions, ranging from chromatin organization, telomere maintenance to DNA replication and repair, a tight functional relationship between HP1 and the MRN complex has never been elucidated. Here we show that the Drosophila HP1a protein binds to the MRN complex through its chromoshadow domain (CSD). In addition, loss of any of the MRN members reduces HP1a levels indicating that the MRN complex acts as regulator of HP1a stability. Moreover, overexpression of HP1a in nbs (but not in rad50 or mre11) mutant cells drastically reduces DNA damage associated with the loss of Nbs suggesting that HP1a and Nbs work in concert to maintain chromosome integrity in flies. We have also found that human HP1α and NBS1 interact with each other and that, similarly to Drosophila, siRNA-mediated inhibition of NBS1 reduces HP1α levels in human cultured cells. Surprisingly, fibroblasts from Nijmegen Breakage Syndrome (NBS) patients, carrying the 657del5 hypomorphic mutation in NBS1 and expressing the p26 and p70 NBS1 fragments, accumulate HP1α indicating that, differently from NBS1 knockout cells, the presence of truncated NBS1 extends HP1α turnover and/or promotes its stability. Remarkably, an siRNA-mediated reduction of HP1α in NBS fibroblasts decreases the hypersensitivity to irradiation, a characteristic of the NBS syndrome. Overall, our data provide an unanticipated evidence of a close interaction between HP1 and NBS1 that is essential for genome stability and point up HP1α as a potential target to counteract chromosome instability in NBS patient cells.
- Published
- 2019
4. The histone deacetylase Rpd3 regulates the heterochromatin structure of Drosophila telomeres
- Author
-
Giosalba Burgio, Antonia M. R. Ingrassia, Francesca Cipressa, Davide Corona, Giovanni Cenci, Burgio, G, Cipressa, F, Ingrassia, AM, Cenci, G, and Corona, D
- Subjects
Telomere-binding protein ,Genetics ,Epigenomics ,Male ,Histone deacetylase 5 ,Histone deacetylase 2 ,HDAC11 ,Histone Deacetylase 1 ,Cell Biology ,Biology ,Telomere ,Histone H4 ,Telomere Homeostasis ,Drosophila melanogaster ,Heterochromatin ,Histone H2A ,histone deacetylase ,Histone code ,Animals ,Drosophila Proteins ,animals ,article ,chromosome aberration ,chromosome structure ,drosophila ,drosophila melanogaster ,drosophila proteins ,enzyme activity ,epigenetics ,epigenomics ,eukaryota ,heterochromatin ,histone acetylation ,histone deacetylase 1 ,histone deacetylase rpd 3 ,histone methylation ,male ,mammalia ,nonhuman ,polytene chromosome ,priority journal ,regulatory mechanism ,telomere ,unclassified drug ,Polytene Chromosomes - Abstract
Telomeres are specialized structures at the end of eukaryotic chromosomes that are required to preserve genome integrity, chromosome stability and nuclear architecture. Telomere maintenance and function are established epigenetically in several eukaryotes. However, the exact chromatin enzymatic modifications regulating telomere homeostasis are poorly understood. In Drosophila melanogaster, telomere length and stability are maintained through the retrotransposition of specialized telomeric sequences and by the specific loading of protecting capping proteins, respectively. Here, we show that the loss of the essential and evolutionarily conserved histone deacetylase Rpd3, the homolog of mammalian HDAC1, causes aberrant telomeric fusions on polytene chromosome ends. Remarkably, these telomere fusion defects are associated with a marked decrease of histone H4 acetylation, as well as an accumulation of heterochromatic epigenetic marks at telomeres, including histone H3K9 trimethylation and the heterochromatic protein HP2. Our work suggests that Drosophila telomere structure is epigenetically regulated by the histone deacetylase Rpd3.
- Published
- 2011
5. Co-amplification of CBX3 with EGFR or RAC1 in human cancers corroborated by a conserved genetic interaction among the genes.
- Author
-
Bosso G, Cipressa F, Tullo L, and Cenci G
- Abstract
Chromobox Protein 3 (CBX3) overexpression is a common event occurring in cancer, promotes cancer cell proliferation and represents a poor prognosis marker in a plethora of human cancers. Here we describe that a wide spectrum of human cancers harbors a co-amplification of CBX3 gene with either EGFR or RAC1, which yields a statistically significant increase of both mRNA and protein levels of CBX3, EGFR and RAC1. We also reveal that the simultaneous overexpression of CBX3, RAC1 and EGFR gene products correlates with a worse prognosis compared to the condition when CBX3, RAC1 and EGFR are singularly upregulated. Furthermore, we also show that a co-occurrence of low-grade amplification, in addition to high-grade amplification, between CBX3 and EGFR or RAC1 is associated with a reduced patient lifespan. Finally, we find that CBX3 and RAC1/EGFR genetically interact in the model organism Drosophila melanogaster, suggesting that the simultaneous overexpression as well as well the co-occurrence of high- or low-grade copy number alterations in these genes is not accidental and could reflect evolutionarily conserved functional relationships., (© 2023. Cell Death Differentiation Association (ADMC).)
- Published
- 2023
- Full Text
- View/download PDF
6. C9orf72 Toxic Species Affect ArfGAP-1 Function.
- Author
-
Rossi S, Di Salvio M, Balì M, De Simone A, Apolloni S, D'Ambrosi N, Arisi I, Cipressa F, Cozzolino M, and Cestra G
- Subjects
- Animals, Humans, Mice, ADP-Ribosylation Factor 1 metabolism, Drosophila genetics, Drosophila metabolism, RNA metabolism, RNA, Messenger genetics, Amyotrophic Lateral Sclerosis metabolism, C9orf72 Protein genetics, C9orf72 Protein metabolism, GTPase-Activating Proteins genetics, GTPase-Activating Proteins metabolism
- Abstract
Compelling evidence indicates that defects in nucleocytoplasmic transport contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). In particular, hexanucleotide (G4C2) repeat expansions in C9orf72 , the most common cause of genetic ALS, have a widespread impact on the transport machinery that regulates the nucleocytoplasmic distribution of proteins and RNAs. We previously reported that the expression of G4C2 hexanucleotide repeats in cultured human and mouse cells caused a marked accumulation of poly(A) mRNAs in the cell nuclei. To further characterize the process, we set out to systematically identify the specific mRNAs that are altered in their nucleocytoplasmic distribution in the presence of C9orf72 -ALS RNA repeats. Interestingly, pathway analysis showed that the mRNAs involved in membrane trafficking are particularly enriched among the identified mRNAs. Most importantly, functional studies in cultured cells and Drosophila indicated that C9orf72 toxic species affect the membrane trafficking route regulated by ADP-Ribosylation Factor 1 GTPase Activating Protein (ArfGAP-1), which exerts its GTPase-activating function on the small GTPase ADP-ribosylation factor 1 to dissociate coat proteins from Golgi-derived vesicles. We demonstrate that the function of ArfGAP-1 is specifically affected by expanded C9orf72 RNA repeats, as well as by C9orf72 -related dipeptide repeat proteins (C9-DPRs), indicating the retrograde Golgi-to-ER vesicle-mediated transport as a target of C9orf72 toxicity.
- Published
- 2023
- Full Text
- View/download PDF
7. Identification of the Telomere elongation Mutation in Drosophila .
- Author
-
Reddy HM, Randall TA, Cipressa F, Porrazzo A, Cenci G, Frydrychova RC, and Mason JM
- Subjects
- Animals, Gene Products, gag genetics, Telomere genetics, Mutation genetics, Drosophila genetics, Drosophila melanogaster genetics
- Abstract
Telomeres in Drosophila melanogaster , which have inspired a large part of Sergio Pimpinelli work, are similar to those of other eukaryotes in terms of their function. Yet, their length maintenance relies on the transposition of the specialized retrotransposons Het-A , TART , and TAHRE , rather than on the activity of the enzyme telomerase as it occurs in most other eukaryotic organisms. The length of the telomeres in Drosophila thus depends on the number of copies of these transposable elements. Our previous work has led to the isolation of a dominant mutation, Tel
1 , that caused a several-fold elongation of telomeres. In this study, we molecularly identified the Tel1 mutation by a combination of transposon-induced, site-specific recombination and next-generation sequencing. Recombination located Tel1 to a 15 kb region in 92A. Comparison of the DNA sequence in this region with the Drosophila Genetic Reference Panel of wild-type genomic sequences delimited Tel1 to a 3 bp deletion inside intron 8 of Ino80. Furthermore, CRISPR/Cas9-induced deletions surrounding the same region exhibited the Tel1 telomere phenotype, confirming a strict requirement of this intron 8 gene sequence for a proper regulation of Drosophila telomere length.- Published
- 2022
- Full Text
- View/download PDF
8. Biallelic mutations in RNF220 cause laminopathies featuring leukodystrophy, ataxia and deafness.
- Author
-
Sferra A, Fortugno P, Motta M, Aiello C, Petrini S, Ciolfi A, Cipressa F, Moroni I, Leuzzi V, Pieroni L, Marini F, Boespflug Tanguy O, Eymard-Pierre E, Danti FR, Compagnucci C, Zambruno G, Brusco A, Santorelli FM, Chiapparini L, Francalanci P, Loizzo AL, Tartaglia M, Cestra G, and Bertini E
- Subjects
- Adolescent, Amino Acid Sequence, Animals, Ataxia diagnosis, COS Cells, Child, Chlorocebus aethiops, Deafness diagnosis, Drosophila, Female, HEK293 Cells, Humans, Laminopathies diagnosis, Male, Pedigree, Young Adult, Alleles, Ataxia genetics, Deafness genetics, Laminopathies genetics, Mutation genetics, Ubiquitin-Protein Ligases genetics
- Abstract
Leukodystrophies are a heterogeneous group of rare inherited disorders that mostly involve the white matter of the CNS. These conditions are characterized by primary glial cell and myelin sheath pathology of variable aetiology, which causes secondary axonal degeneration, generally emerging with disease progression. Whole exome sequencing performed in five large consanguineous nuclear families allowed us to identify homozygosity for two recurrent missense variants affecting highly conserved residues of RNF220 as the causative event underlying a novel form of leukodystrophy with ataxia and sensorineural deafness. We report these two homozygous missense variants (p.R363Q and p.R365Q) in the ubiquitin E3 ligase RNF220 as the underlying cause of this novel form of leukodystrophy with ataxia and sensorineural deafness that includes fibrotic cardiomyopathy and hepatopathy as associated features in seven consanguineous families. Mass spectrometry analysis identified lamin B1 as the RNF220 binding protein and co-immunoprecipitation experiments demonstrated reduced binding of both RNF220 mutants to lamin B1. We demonstrate that RNF220 silencing in Drosophila melanogaster specifically affects proper localization of lamin Dm0, the fly lamin B1 orthologue, promotes its aggregation and causes a neurodegenerative phenotype, strongly supporting the functional link between RNF220 and lamin B1. Finally, we demonstrate that RNF220 plays a crucial role in the maintenance of nuclear morphology; mutations in primary skin fibroblasts determine nuclear abnormalities such as blebs, herniations and invaginations, which are typically observed in cells of patients affected by laminopathies. Overall, our data identify RNF220 as a gene implicated in leukodystrophy with ataxia and sensorineural deafness and document a critical role of RNF220 in the regulation of nuclear lamina. Our findings provide further evidence on the direct link between nuclear lamina dysfunction and neurodegeneration., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
9. Underground Radiobiology: A Perspective at Gran Sasso National Laboratory.
- Author
-
Esposito G, Anello P, Ampollini M, Bortolin E, De Angelis C, D'Imperio G, Dini V, Nuccetelli C, Quattrini MC, Tomei C, Ianni A, Balata M, Carinci G, Chiti M, Frasciello O, Cenci G, Cipressa F, De Gregorio A, Porrazzo A, Tabocchini MA, Satta L, and Morciano P
- Subjects
- Animals, Drosophila melanogaster, Italy, Radiobiology, Laboratories, Radiation Protection
- Abstract
Scientific community and institutions (e. g., ICRP) consider that the Linear No-Threshold (LNT) model, which extrapolates stochastic risk at low dose/low dose rate from the risk at moderate/high doses, provides a prudent basis for practical purposes of radiological protection. However, biological low dose/dose rate responses that challenge the LNT model have been highlighted and important dowels came from radiobiology studies conducted in Deep Underground Laboratories (DULs). These extreme ultra-low radiation environments are ideal locations to conduct below-background radiobiology experiments, interesting from basic and applied science. The INFN Gran Sasso National Laboratory (LNGS) (Italy) is the site where most of the underground radiobiological data has been collected so far and where the first in vivo underground experiment was carried out using Drosophila melanogaster as model organism. Presently, many DULs around the world have implemented dedicated programs, meetings and proposals. The general message coming from studies conducted in DULs using protozoan, bacteria, mammalian cells and organisms (flies, worms, fishes) is that environmental radiation may trigger biological mechanisms that can increase the capability to cope against stress. However, several issues are still open, among them: the role of the quality of the radiation spectrum in modulating the biological response, the dependence on the biological endpoint and on the model system considered, the overall effect at organism level (detrimental or beneficial). At LNGS, we recently launched the RENOIR experiment aimed at improving knowledge on the environmental radiation spectrum and to investigate the specific role of the gamma component on the biological response of Drosophila melanogaster ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Esposito, Anello, Ampollini, Bortolin, De Angelis, D'Imperio, Dini, Nuccetelli, Quattrini, Tomei, Ianni, Balata, Carinci, Chiti, Frasciello, Cenci, Cipressa, De Gregorio, Porrazzo, Tabocchini, Satta and Morciano.)
- Published
- 2020
- Full Text
- View/download PDF
10. The Drosophila Citrate Lyase Is Required for Cell Division during Spermatogenesis.
- Author
-
Di Giorgio ML, Morciano P, Bucciarelli E, Porrazzo A, Cipressa F, Saraniero S, Manzi D, Rong YS, and Cenci G
- Subjects
- Animals, Male, Multienzyme Complexes genetics, Oxo-Acid-Lyases genetics, Cell Division genetics, Drosophila melanogaster enzymology, Multienzyme Complexes metabolism, Oxo-Acid-Lyases metabolism, Spermatogenesis genetics
- Abstract
The Drosophila melanogaster DmATPCL gene encodes for the human ATP Citrate Lyase (ACL) ortholog, a metabolic enzyme that from citrate generates glucose-derived Acetyl-CoA, which fuels central biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine, and the acetylation of proteins and histones. We had previously reported that, although loss of Drosophila ATPCL reduced levels of Acetyl-CoA, unlike its human counterpart, it does not affect global histone acetylation and gene expression, suggesting that its role in histone acetylation is either partially redundant in Drosophila or compensated by alternative pathways. Here, we describe that depletion of DmATPCL affects spindle organization, cytokinesis, and fusome assembly during male meiosis, revealing an unanticipated role for DmATPCL during spermatogenesis. We also show that DmATPCL mutant meiotic phenotype is in part caused by a reduction of fatty acids, but not of triglycerides or cholesterol, indicating that DmATPCL-derived Acetyl-CoA is predominantly devoted to the biosynthesis of fatty acids during spermatogenesis. Collectively, our results unveil for the first time an involvement for DmATPCL in the regulation of meiotic cell division, which is likely conserved in human cells., Competing Interests: The authors declare no conflict of interest.
- Published
- 2020
- Full Text
- View/download PDF
11. NBS1 interacts with HP1 to ensure genome integrity.
- Author
-
Bosso G, Cipressa F, Moroni ML, Pennisi R, Albanesi J, Brandi V, Cugusi S, Renda F, Ciapponi L, Polticelli F, Antoccia A, di Masi A, and Cenci G
- Subjects
- Animals, Chromobox Protein Homolog 5, DNA Damage genetics, Drosophila melanogaster genetics, Female, Fibroblasts metabolism, Fibroblasts pathology, Gene Expression Regulation, Genome, Insect genetics, Humans, Male, Mutation genetics, Nijmegen Breakage Syndrome genetics, Nijmegen Breakage Syndrome pathology, Cell Cycle Proteins genetics, Chromosomal Proteins, Non-Histone genetics, Drosophila Proteins genetics, Endodeoxyribonucleases genetics, Exodeoxyribonucleases genetics, Genomic Instability genetics, Nuclear Proteins genetics
- Abstract
Heterochromatin Protein 1 (HP1) and the Mre11-Rad50-Nbs1 (MRN) complex are conserved factors that play crucial role in genome stability and integrity. Despite their involvement in overlapping cellular functions, ranging from chromatin organization, telomere maintenance to DNA replication and repair, a tight functional relationship between HP1 and the MRN complex has never been elucidated. Here we show that the Drosophila HP1a protein binds to the MRN complex through its chromoshadow domain (CSD). In addition, loss of any of the MRN members reduces HP1a levels indicating that the MRN complex acts as regulator of HP1a stability. Moreover, overexpression of HP1a in nbs (but not in rad50 or mre11) mutant cells drastically reduces DNA damage associated with the loss of Nbs suggesting that HP1a and Nbs work in concert to maintain chromosome integrity in flies. We have also found that human HP1α and NBS1 interact with each other and that, similarly to Drosophila, siRNA-mediated inhibition of NBS1 reduces HP1α levels in human cultured cells. Surprisingly, fibroblasts from Nijmegen Breakage Syndrome (NBS) patients, carrying the 657del5 hypomorphic mutation in NBS1 and expressing the p26 and p70 NBS1 fragments, accumulate HP1α indicating that, differently from NBS1 knockout cells, the presence of truncated NBS1 extends HP1α turnover and/or promotes its stability. Remarkably, an siRNA-mediated reduction of HP1α in NBS fibroblasts decreases the hypersensitivity to irradiation, a characteristic of the NBS syndrome. Overall, our data provide an unanticipated evidence of a close interaction between HP1 and NBS1 that is essential for genome stability and point up HP1α as a potential target to counteract chromosome instability in NBS patient cells.
- Published
- 2019
- Full Text
- View/download PDF
12. Phenotypic characterization of diamond (dind), a Drosophila gene required for multiple aspects of cell division.
- Author
-
Graziadio L, Palumbo V, Cipressa F, Williams BC, Cenci G, Gatti M, Goldberg ML, and Bonaccorsi S
- Subjects
- Animals, Animals, Genetically Modified, Brain cytology, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cell Division genetics, Chromosome Breakage, Chromosome Segregation, Drosophila genetics, Drosophila Proteins metabolism, Green Fluorescent Proteins genetics, Larva cytology, Male, Mutation, Phenotype, Spermatocytes cytology, Chromosomes, Insect genetics, Drosophila cytology, Drosophila Proteins genetics, Meiosis, Spermatocytes physiology
- Abstract
Many genes are required for the assembly of the mitotic apparatus and for proper chromosome behavior during mitosis and meiosis. A fruitful approach to elucidate the mechanisms underlying cell division is the accurate phenotypic characterization of mutations in these genes. Here, we report the identification and characterization of diamond (dind), an essential Drosophila gene required both for mitosis of larval brain cells and for male meiosis. Larvae homozygous for any of the five EMS-induced mutations die in the third-instar stage and exhibit multiple mitotic defects. Mutant brain cells exhibit poorly condensed chromosomes and frequent chromosome breaks and rearrangements; they also show centriole fragmentation, disorganized mitotic spindles, defective chromosome segregation, endoreduplicated metaphases, and hyperploid and polyploid cells. Comparable phenotypes occur in mutant spermatogonia and spermatocytes. The dind gene encodes a non-conserved protein with no known functional motifs. Although the Dind protein exhibits a rather diffuse localization in both interphase and mitotic cells, fractionation experiments indicate that some Dind is tightly associated with the chromatin. Collectively, these results suggest that loss of Dind affects chromatin organization leading to defects in chromosome condensation and integrity, which in turn affect centriole stability and spindle assembly. However, our results do not exclude the possibility that Dind directly affects some behaviors of the spindle and centrosomes.
- Published
- 2018
- Full Text
- View/download PDF
13. The Drosophila telomere-capping protein Verrocchio binds single-stranded DNA and protects telomeres from DNA damage response.
- Author
-
Cicconi A, Micheli E, Vernì F, Jackson A, Gradilla AC, Cipressa F, Raimondo D, Bosso G, Wakefield JG, Ciapponi L, Cenci G, Gatti M, Cacchione S, and Raffa GD
- Subjects
- Animals, Chromosomal Proteins, Non-Histone physiology, DNA Repair, DNA, Single-Stranded ultrastructure, Drosophila genetics, Drosophila Proteins chemistry, Drosophila Proteins physiology, Drosophila Proteins ultrastructure, Microscopy, Atomic Force, Protein Domains, Protein Multimerization, Replication Protein A metabolism, Telomere-Binding Proteins chemistry, Telomere-Binding Proteins ultrastructure, DNA Damage, DNA, Single-Stranded metabolism, Drosophila Proteins metabolism, Telomere metabolism, Telomere-Binding Proteins metabolism
- Abstract
Drosophila telomeres are sequence-independent structures maintained by transposition to chromosome ends of three specialized retroelements rather than by telomerase activity. Fly telomeres are protected by the terminin complex that includes the HOAP, HipHop, Moi and Ver proteins. These are fast evolving, non-conserved proteins that localize and function exclusively at telomeres, protecting them from fusion events. We have previously suggested that terminin is the functional analogue of shelterin, the multi-protein complex that protects human telomeres. Here, we use electrophoretic mobility shift assay (EMSA) and atomic force microscopy (AFM) to show that Ver preferentially binds single-stranded DNA (ssDNA) with no sequence specificity. We also show that Moi and Ver form a complex in vivo. Although these two proteins are mutually dependent for their localization at telomeres, Moi neither binds ssDNA nor facilitates Ver binding to ssDNA. Consistent with these results, we found that Ver-depleted telomeres form RPA and γH2AX foci, like the human telomeres lacking the ssDNA-binding POT1 protein. Collectively, our findings suggest that Drosophila telomeres possess a ssDNA overhang like the other eukaryotes, and that the terminin complex is architecturally and functionally similar to shelterin., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2017
- Full Text
- View/download PDF
14. A role for Separase in telomere protection.
- Author
-
Cipressa F, Morciano P, Bosso G, Mannini L, Galati A, Raffa GD, Cacchione S, Musio A, and Cenci G
- Subjects
- Animals, Chromosomal Proteins, Non-Histone genetics, Chromosomal Proteins, Non-Histone metabolism, Drosophila, Drosophila Proteins genetics, Humans, Nuclear Proteins genetics, Nuclear Proteins metabolism, Separase genetics, Telomere genetics, Drosophila Proteins metabolism, Separase metabolism, Telomere metabolism
- Abstract
Drosophila telomeres are elongated by transposition of specialized retroelements rather than telomerase activity and are assembled independently of the sequence. Fly telomeres are protected by the terminin complex that localizes and functions exclusively at telomeres and by non-terminin proteins that do not serve telomere-specific functions. We show that mutations in the Drosophila Separase encoding gene Sse lead not only to endoreduplication but also telomeric fusions (TFs), suggesting a role for Sse in telomere capping. We demonstrate that Separase binds terminin proteins and HP1, and that it is enriched at telomeres. Furthermore, we show that loss of Sse strongly reduces HP1 levels, and that HP1 overexpression in Sse mutants suppresses TFs, suggesting that TFs are caused by a HP1 diminution. Finally, we find that siRNA-induced depletion of ESPL1, the Sse human orthologue, causes telomere dysfunction and HP1 level reduction in primary fibroblasts, highlighting a conserved role of Separase in telomere protection.
- Published
- 2016
- Full Text
- View/download PDF
15. Effete, an E2 ubiquitin-conjugating enzyme with multiple roles in Drosophila development and chromatin organization.
- Author
-
Cipressa F and Cenci G
- Subjects
- Animals, Apoptosis genetics, Drosophila growth & development, Drosophila metabolism, Drosophila Proteins genetics, Drosophila Proteins metabolism, Female, Male, Telomere Homeostasis genetics, Ubiquitin-Conjugating Enzymes genetics, Ubiquitin-Conjugating Enzymes metabolism, Chromatin metabolism, Chromatin Assembly and Disassembly, Drosophila genetics, Drosophila Proteins physiology, Ubiquitin-Conjugating Enzymes physiology
- Abstract
The Drosophila effete gene encodes an extremely conserved class I E2 ubiquitin-conjugating enzyme. Growing evidence indicates that Eff is involved in many cellular processes including eye development, maintenance of female germline stem cells, and regulation of apoptosis. Eff is also a major component of Drosophila chromatin and it is particularly enriched in chromatin with repressive properties. In addition, Eff is required for telomere protection and to prevent telomere fusion. Consistent with its multiple roles in chromatin maintenance, Eff is also one of the rare factors that modulate both telomere-induced and heterochromatin-induced position effect variegation.
- Published
- 2013
- Full Text
- View/download PDF
16. Effete, a Drosophila chromatin-associated ubiquitin-conjugating enzyme that affects telomeric and heterochromatic position effect variegation.
- Author
-
Cipressa F, Romano S, Centonze S, zur Lage PI, Vernì F, Dimitri P, Gatti M, and Cenci G
- Subjects
- Animals, Drosophila enzymology, Drosophila metabolism, Drosophila Proteins metabolism, Heterochromatin metabolism, Mutation, Polytene Chromosomes genetics, Polytene Chromosomes metabolism, Telomere metabolism, Telomere-Binding Proteins genetics, Telomere-Binding Proteins metabolism, Ubiquitin-Conjugating Enzymes metabolism, Chromosomal Position Effects, Drosophila genetics, Drosophila Proteins genetics, Heterochromatin genetics, Telomere genetics, Ubiquitin-Conjugating Enzymes genetics
- Abstract
Drosophila telomeres are elongated by the transposition of telomere-specific retrotransposons rather than telomerase activity. Proximal to the terminal transposon array, Drosophila chromosomes contain several kilobases of a complex satellite DNA termed telomere-associated sequences (TASs). Reporter genes inserted into or next to the TAS are silenced through a mechanism called telomere position effect (TPE). TPE is reminiscent of the position effect variegation (PEV) induced by Drosophila constitutive heterochromatin. However, most genes that modulate PEV have no effect on TPE, and systematic searches for TPE modifiers have so far identified only a few dominant suppressors. Surprisingly, only a few of the genes required to prevent telomere fusion have been tested for their effect on TPE. Here, we show that with the exception of the effete (eff; also called UbcD1) mutant alleles, none of the tested mutations at the other telomere fusion genes affects TPE. We also found that mutations in eff, which encodes a class I ubiquitin-conjugating enzyme, act as suppressors of PEV. Thus, eff is one of the rare genes that can modulate both TPE and PEV. Immunolocalization experiments showed that Eff is a major constituent of polytene chromosomes. Eff is enriched at several euchromatic bands and interbands, the TAS regions, and the chromocenter. Our results suggest that Eff associates with different types of chromatin affecting their abilities to regulate gene expression.
- Published
- 2013
- Full Text
- View/download PDF
17. The histone deacetylase Rpd3 regulates the heterochromatin structure of Drosophila telomeres.
- Author
-
Burgio G, Cipressa F, Ingrassia AM, Cenci G, and Corona DF
- Subjects
- Animals, Drosophila melanogaster metabolism, Epigenomics, Male, Polytene Chromosomes, Drosophila Proteins metabolism, Drosophila melanogaster genetics, Heterochromatin metabolism, Histone Deacetylase 1 metabolism, Telomere metabolism
- Abstract
Telomeres are specialized structures at the end of eukaryotic chromosomes that are required to preserve genome integrity, chromosome stability and nuclear architecture. Telomere maintenance and function are established epigenetically in several eukaryotes. However, the exact chromatin enzymatic modifications regulating telomere homeostasis are poorly understood. In Drosophila melanogaster, telomere length and stability are maintained through the retrotransposition of specialized telomeric sequences and by the specific loading of protecting capping proteins, respectively. Here, we show that the loss of the essential and evolutionarily conserved histone deacetylase Rpd3, the homolog of mammalian HDAC1, causes aberrant telomeric fusions on polytene chromosome ends. Remarkably, these telomere fusion defects are associated with a marked decrease of histone H4 acetylation, as well as an accumulation of heterochromatic epigenetic marks at telomeres, including histone H3K9 trimethylation and the heterochromatic protein HP2. Our work suggests that Drosophila telomere structure is epigenetically regulated by the histone deacetylase Rpd3.
- Published
- 2011
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.