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

Clémence Claussin, Michael Chang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)
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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.

Original languageEnglish
Article number1006176
Number of pages19
JournalPLoS genetics
Volume12
Issue number7
DOIs
Publication statusPublished - Jul-2016

Keywords

  • BREAK-INDUCED REPLICATION
  • DOUBLE-STRAND BREAKS
  • POSTREPLICATION REPAIR
  • MITOTIC RECOMBINATION
  • LENGTH HOMEOSTASIS
  • H3K56 ACETYLATION
  • REPEAT DIVERGENCE
  • GENOME INTEGRITY
  • DNA-REPLICATION
  • YEAST TELOMERES

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