| Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres. | |
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MedLine Citation:
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PMID: 20890289 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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During replicative aging of primary cells morphological transformations occur, the expression pattern is altered and chromatin changes globally. Here we show that chronic damage signals, probably caused by telomere processing, affect expression of histones and lead to their depletion. We investigated the abundance and cell cycle expression of histones and histone chaperones and found defects in histone biosynthesis during replicative aging. Simultaneously, epigenetic marks were redistributed across the phases of the cell cycle and the DNA damage response (DDR) machinery was activated. The age-dependent reprogramming affected telomeric chromatin itself, which was progressively destabilized, leading to a boost of the telomere-associated DDR with each successive cell cycle. We propose a mechanism in which changes in the structural and epigenetic integrity of telomeres affect core histones and their chaperones, enforcing a self-perpetuating pathway of global epigenetic changes that ultimately leads to senescence. |
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Authors:
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Roderick J O'Sullivan; Stefan Kubicek; Stuart L Schreiber; Jan Karlseder |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-03 |
Journal Detail:
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Title: Nature structural & molecular biology Volume: 17 ISSN: 1545-9985 ISO Abbreviation: Nat. Struct. Mol. Biol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-06 Completed Date: 2010-11-16 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 101186374 Medline TA: Nat Struct Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1218-25 Citation Subset: IM |
Affiliation:
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The Salk Institute for Biological Studies, Molecular and Cellular Biology Department, La Jolla, California, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Bleomycin
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toxicity Cell Aging / physiology* Cell Line Chromatin / metabolism* Chromatin Immunoprecipitation DNA Damage* DNA Replication Epigenesis, Genetic Fibroblasts / cytology, drug effects, metabolism* Histones / biosynthesis* Humans Methylation Nuclear Proteins / biosynthesis, genetics Oncogene Proteins, Viral / physiology Papillomavirus E7 Proteins / physiology Protein Processing, Post-Translational Repressor Proteins / physiology Retinoblastoma Protein / physiology Telomere / physiology* Tumor Suppressor Protein p53 / physiology mRNA Cleavage and Polyadenylation Factors / biosynthesis, genetics |
| Grant Support | |
ID/Acronym/Agency:
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R01 AG025837/AG/NIA NIH HHS; R01 AG025837-03/AG/NIA NIH HHS; R01 AG025837-04/AG/NIA NIH HHS; R01 GM06525/GM/NIGMS NIH HHS; R01 GM069525-04/GM/NIGMS NIH HHS; R01 GM069525-05/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chromatin; 0/E6 protein, Human papillomavirus type 16; 0/Histones; 0/Nuclear Proteins; 0/Oncogene Proteins, Viral; 0/Papillomavirus E7 Proteins; 0/Repressor Proteins; 0/Retinoblastoma Protein; 0/SLBP protein, human; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/mRNA Cleavage and Polyadenylation Factors; 0/oncogene protein E7, Human papillomavirus type 16; 11056-06-7/Bleomycin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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