Abstract
DNA double strand break (DSB) is one of the major damages that cause genome instability and cellular aging. The homologous recombination (HR)-mediated repair of DSBs plays an essential role in assurance of genome stability and cell longevity. Telomeres resemble DSBs and are competent for HR. Here we show that in budding yeast Saccharomyces cerevisiae telomere recombination elicits genome instability and accelerates cellular aging. Inactivation of KEOPS subunit Cgi121 specifically inhibits telomere recombination, and significantly extends cell longevity in both telomerase-positive and pre-senescing telomerase-negative cells. Deletion of CGI121 in the short-lived yku80tel mutant restores lifespan to cgi121Δ level, supporting the function of Cgi121 in telomeric single-stranded DNA generation and thus in promotion of telomere recombination. Strikingly, inhibition of telomere recombination is able to further slow down the aging process in long-lived fob1Δ cells, in which rDNA recombination is restrained. Our study indicates that HR activity at telomeres interferes with telomerase to pose a negative impact on cellular longevity.
Highlights
Aging is generally defined as the time-dependent functional decline and increased mortality in most living organisms
homologous recombination (HR) is crucial for DNA repair and genome integrity maintenance, and is generally believed to be essential for assurance of cell longevity
We show that HR at yeast telomeres elicits genome instability and accelerates
Summary
Aging is generally defined as the time-dependent functional decline and increased mortality in most living organisms. In order to elucidate how aging is influenced by intrinsic cellular traits, researchers have developed and employed various model organisms including yeast, worm, fly, fish, mouse and monkey to study the pathways that affect aging. The single-cell organism, budding yeast Saccharomyces cerevisiae represents a widely used tool for aging study [1,2,3]. A single yeast mother cell can only generate a limited number of daughter cells before its mitotic arrest [4]. This aging-associated phenotype is called replicative aging [5]. The organismal aging for multicellular species is likely (or at least partially) to be attributed to cellular aging in their corresponding organs and/or tissues
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
