Multiple Rad52-Mediated Homology-Directed Repair Mechanisms Are Required to Prevent Telomere Attrition-Induced Senescence in Saccharomyces cerevisiaeClaussin, C. & Chang, M., Jul-2016, In : PLoS genetics. 12, 7, 19 p., 1006176.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||19|
|Publication status||Published - Jul-2016|
- BREAK-INDUCED REPLICATION, DOUBLE-STRAND BREAKS, POSTREPLICATION REPAIR, MITOTIC RECOMBINATION, LENGTH HOMEOSTASIS, H3K56 ACETYLATION, REPEAT DIVERGENCE, GENOME INTEGRITY, DNA-REPLICATION, YEAST TELOMERES