Inhibition of Telomere Recombination by Inactivation of KEOPS Subunit Cgi121 Promotes Cell Longevity

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Aging is a general biological process among the living organisms which is affected by environmental stimuli but also genetically controlled. Genome instability is one of the aging hallmarks and has long been implicated as one of the main causal factors in aging. DNA double strand breaks (DSBs) are the most deleterious DNA damages that cause genome instability. To counteract DNA damage of DSBs and maintain high level of genome integrity, cells have evolved powerful repair systems such as homologous recombination (HR). HR is crucial for DNA repair and genome integrity maintenance, and is generally believed to be essential for assurance of cell longevity. Telomeres, the physical ends of eukaryotic linear chromosomes, are preferentially elongated by telomerase, a specialized reverse transcriptase, in most cases. However, due to the resemblance of telomeres to DSBs, HR can not be eliminated but rather readily takes place on telomeres, even in the presence of telomerase. Here we show that HR at yeast telomeres elicits genome instability and accelerates cellular aging. Inactivation of the evolutionarily conserved KEOPS complex subunit Cgi121 specifically inhibits telomere HR and results in extremely long lifespan, indicating a dark side of HR in longevity regulation.

Vyšlo v časopise: Inhibition of Telomere Recombination by Inactivation of KEOPS Subunit Cgi121 Promotes Cell Longevity. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005071
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005071

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