Zhenfang Wu
Jin-Qiu Zhou
aCAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China
bSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
More InformationCorresponding author: E-mail address: zhenfang.wu@sibcb.ac.cn (Zhenfang Wu);E-mail address: jqzhou@sibcb.ac.cn (Jin-Qiu Zhou)
Received Date: 2018-06-02
Accepted Date:2018-09-10
Rev Recd Date:2018-09-06
Available Online: 2018-09-19 Publish Date:2018-09-20
Abstract
Abstract
It has been well documented that Tel1 positively regulates telomere-end resection by promoting Mre11-Rad50-Xrs2 (MRX) activity, while Rif2 negatively regulates telomere-end resection by inhibiting MRX activity. At uncapped telomeres, whether Tel1 or Rif2 plays any role remains largely unknown. In this work, we examined the roles of Tel1 and Rif2 at uncapped telomeres in yku70Δ and/or cdc13-1 mutant cells cultured at non-permissive temperature. We found that deletion of TEL1 exacerbates the temperature sensitivity of both yku70Δ and cdc13-1?cells. Further epistasis analysis indicated that MRX and Tel1 function in the same pathway in telomere protection. Consistently, TEL1 deletion increases accumulation of Exo1-dependent telomeric single-stranded DNA (ssDNA) at uncapped telomeres, which stimulates checkpoint-dependent cell cycle arrest. Moreover, TEL1 deletion in yku70Δ cells facilitates Rad51-dependent Y′ recombination. In contrast, RIF2 deletion in yku70Δ cells decreases the accumulation of telomeric ssDNA after 8?h of incubation at the non-permissive temperature of 37?°C and suppresses the temperature sensitivity of yku70Δ cells, likely due to the increase of Mre11 association at telomeres. Collectively, our findings indicate that Tel1 and Rif2 regulate telomere protection at uncapped telomeres via their roles in balancing MRX activity in telomere resection.Keywords: Tel1,
Rif2,
MRX,
Uncapped telomeres,
Telomere protection
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