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Mol Microbiol

Title:		Mating type influences chromosome loss and replicative senescence in telomerase-deficient budding yeast by Dnl4-dependent telomere fusion
Author(s):		Meyer DH; Bailis AM;
Address:		"Division of Molecular Biology, Beckman Research Institute of the City of Hope, and City of Hope Graduate School of Biological Sciences, Duarte, CA 91010-0269, USA"
Journal Title:		Mol Microbiol
Year:		2008
Volume:		20080704
Issue:		5
Page Number:		1246 - 1254
DOI:		10.1111/j.1365-2958.2008.06353.x
ISSN/ISBN:		1365-2958 (Electronic) 0950-382X (Print) 0950-382X (Linking)
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 repair in influencing both the kinetics of replicative senescence and the rate of chromosome loss in telomerase-deficient Saccharomyces cerevisiae. 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 are determined by changes in NHEJ-dependent telomere fusion, perhaps through the initiation of the breakage-fusion-bridge cycle"
Keywords:		"Chromosome Deletion Chromosomes, Fungal/genetics/metabolism DNA Ligase ATP DNA Ligases/genetics/*metabolism Gene Expression Regulation, Fungal Mating Factor Microbial Viability Peptides/genetics/*metabolism Recombination, Genetic Saccharomyces cerevisiae/;"
Notes:		"MedlineMeyer, Damon H Bailis, Adam M eng R01 GM057484/GM/NIGMS NIH HHS/ R01 GM057484-09/GM/NIGMS NIH HHS/ GM057484/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England 2008/07/17 Mol Microbiol. 2008 Sep; 69(5):1246-54. doi: 10.1111/j.1365-2958.2008.06353.x. Epub 2008 Jul 4"