AsianScientist (Apr. 14, 2015) – Researchers have found that inhibiting DNA recombination at the telomeres can promote longevity, at least in yeast. Their results have been published in PLOS Genetics.
Homologous recombination is a process used to repair double stranded breaks in DNA, thereby preventing genome instability which is believed to cause aging. The shortening of telomeres, the physical ends of eukaryotic linear chromosomes, has also implicated in aging. However, due to the resemblance of telomeres to DNA double strand breaks (DSBs), homologous recombination can not be eliminated from telomeres.
Professor Zhou Jinqiu and his group at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, has now identified a telomere recombination regulator, the yeast KEOPS subunit Cgi121, as a novel longevity regulator. They showed that inactivation of Cgi121 inhibited telomere recombination and significantly extended the lifespan of yeast.
Previous work by Zhou’s group showed that activation of telomere recombination by depletion of telomerase accelerates cellular aging, suggesting a dark side of telomere recombination on longevity. A subsequent genetic screen for telomere recombination regulators identified several genes required for telomere recombination, including the evolutionarily conserved KEOPS complex.
In the present study, Zhou and colleagues confirmed that telomere recombination accelerates aging and inhibition of homologous recombination at the telomeres restores lifespan. In addition, they found that Cgi121 is specifically required for telomere recombination. Deletion of CGI121 gene compromises telomere recombination efficiency and strikingly extends replicative lifespan.
Notably, Cgi121 does not affect recombination at another highly recombinogenic region, the rDNA region. Inhibition of recombination at telomeres and the rDNA locus causes additive effects on slowing down the aging process. Further characterization revealed that Cgi121 may affect aging by generating telomeric single-strand DNA to promote telomere recombination. This study suggests that recombination activities at telomeres interfere with telomerase to pose a negative effect on cellular longevity.
The article can be found at: Peng et al. (2015) Inhibition Of Telomere Recombination By Inactivation Of KEOPS Subunit Cgi121 Promotes Cell Longevity
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Source: Shanghai Institutes for Biological Sciences.
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