title: Multiple Rad52-Mediated Homology-Directed Repair Mechanisms Are Required to Prevent Telomere Attrition-Induced Senescence in Saccharomyces cerevisiae.
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.
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Clémence
authors.identifier: 0000-0002-0994-3596
authors.initials: C
authors.lastname: Claussin
authors.affiliation: European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Michael
authors.identifier: 0000-0002-1706-3337
authors.initials: M
authors.lastname: Chang
mesh_terms: D002842:Chromatids / Q000378:metabolism; D004260:DNA Repair; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D008856:Microscopy, Fluorescence; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D012854:Sister Chromatid Exchange; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000648:ultrastructure*
chemical_list: D006657:Histones; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase; D008239:Lysine