Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence.

ABSTRACT: Genomic instability is a hallmark of aging tissues. Genomic instability may arise from the inefficient or aberrant function of DNA double-stranded break (DSB) repair. DSBs are repaired by homologous recombination (HR) and nonhomologous DNA end joining (NHEJ). HR is a precise pathway, whereas NHEJ frequently leads to deletions or insertions at the repair site. Here, we used normal human fibroblasts with a chromosomally integrated HR reporter cassette to examine the changes in HR efficiency as cells progress to replicative senescence. We show that HR declines sharply with increasing replicative age, with an up to 38-fold decrease in efficiency in presenescent cells relative to young cells. This decline is not explained by a reduction of the number of cells in S/G(2)/M stage as presenescent c

SUBMITTER: Mao Z 

PROVIDER: S-EPMC3406824 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature