Multiple Rad52-Mediated Homology-Directed Repair Mechanisms Are Required to Prevent Telomere Attrition-Induced Senescence in Saccharomyces cerevisiae

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 ce...

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Bibliographic Details
Published in:PLoS genetics 2016-07, Vol.12 (7), p.e1006176-e1006176
Main Authors: Claussin, Clémence, Chang, Michael
Format: Article
Language:English
Subjects:
Aging
Aging (Biology)
Biology and Life Sciences
Cell division
Chromatids - metabolism
Chromosomes
Deoxyribonucleic acid
DNA
DNA Repair
Gene Expression Regulation, Fungal
Genetic aspects
Genetic recombination
Genotype & phenotype
Histones - chemistry
Lysine - chemistry
Microscopy, Fluorescence
Mutation
Observations
Physiological aspects
Plasmids - metabolism
Polymerase Chain Reaction
Rad52 DNA Repair and Recombination Protein - genetics
Rad52 DNA Repair and Recombination Protein - metabolism
Recombination, Genetic
Research and Analysis Methods
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Senescence
Sister Chromatid Exchange
Telomerase
Telomerase - genetics
Telomere - ultrastructure
Telomeres
Yeast
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1006176