Meyer DH and Bailis AM (2008) Mating type influences chromosome loss and replicative senescence in telomerase-deficient budding yeast by Dnl4-dependent telomere fusion. Mol Microbiol 69(5):1246-54
Abstract: As we age, the majority of our cells gradually lose the capacity to divide because of replicative senescence that results from the inability to replicate the ends of chromosomes. The timing of senescence is dependent on the length of telomeric DNA, which elicits a checkpoint signal when critically short. Critically short telomeres also become vulnerable to deleterious rearrangements, end degradation and telomere-telomere fusions. Here we report a novel role of non-homologous end joining (NHEJ), a pathway of double-strand break (DSB) repair in influencing both the kinetics of replicative senescence and the rate of chromosome loss in telomerase-deficient Saccharomycescerevisiae. In telomerase-deficient cells, the absence of NHEJ delays replicative senescence, decreases loss of viability during senescence, and suppresses senescence-associated chromosome loss and telomere-telomere fusion. Differences in mating-type gene expression in haploid and diploid cells affect NHEJ function, resulting in distinct kinetics of replicative senescence. These results suggest that the differences in the kinetics of replicative senescence in haploid and diploid telomerase-deficient yeast is determined by changes in NHEJ-dependent telomere fusion, perhaps through the initiation of the breakage-fusion-bridge (BFB) cycle.
|Status: Published||Type: Journal Article||PubMed ID: 18627461|
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