Abstract
Most human somatic cells express insufficient levels of telomerase, which can result in telomere shortening and eventually senescence, both of which are hallmarks of ageing. Homology-directed repair (HDR) is important for maintaining proper telomere function in yeast and mammals. In Saccharomyces cerevisiae, Rad52 is required for almost all HDR mechanisms, and telomerase-null cells senesce faster in the absence of Rad52. However, its role in preventing accelerated senescence has been unclear. In this study, we make use of rad52 separation-of-function mutants to find that multiple Rad52-mediated HDR mechanisms are required to delay senescence, including break-induced replication and sister chromatid recombination. In addition, we show that misregulation of histone 3 lysine 56 acetylation, which is known to be defective in sister chromatid recombination, also causes accelerated senescence. We propose a model where Rad52 is needed to repair telomere attrition-induced replication stress.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Chromatids / metabolism
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DNA Repair*
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Gene Expression Regulation, Fungal
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Histones / chemistry
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Lysine / chemistry
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Microscopy, Fluorescence
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Mutation
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Plasmids / metabolism
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Polymerase Chain Reaction
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Rad52 DNA Repair and Recombination Protein / genetics*
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Rad52 DNA Repair and Recombination Protein / metabolism
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Recombination, Genetic
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae Proteins / genetics*
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Saccharomyces cerevisiae Proteins / metabolism
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Sister Chromatid Exchange
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Telomerase / genetics
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Telomere / ultrastructure*
Substances
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Histones
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RAD52 protein, S cerevisiae
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Rad52 DNA Repair and Recombination Protein
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Saccharomyces cerevisiae Proteins
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Telomerase
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Lysine
Grants and funding
Work in the Chang lab is supported by a Vidi grant (to MC) from the Netherlands Organisation for Scientific Research (
http://www.nwo.nl/en). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.