SUMOylation regulates telomere length homeostasis by targeting Cdc13

Lisa E. Hang, Xianpeng Liu, Iris Cheung, Yan Yang, Xiaolan Zhao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Telomere length homeostasis is an important aspect of telomere biology. Here, we show that SUMOylation limits telomere length and targets multiple telomere proteins in Saccharomyces cerevisiae. A main target is Cdc13, which both positively and negatively regulates telomerase and confers end protection. We demonstrate that Cdc13 SUMOylation restrains telomerase functions by promoting Cdc13 interaction with the telomerase inhibitor Stn1 without affecting end protection. Mutation of the Cdc13 SUMOylation site (cdc13-snm) lengthens telomeres and reduces the Stn1 interaction, whereas Cdc13-SUMO fusion has the opposite effects. cdc13-snm's effect on telomere length is epistatic with stn1, but not with yku70, tel1 or est1 alleles, and is suppressed by Stn1 overexpression. Cdc13 SUMOylation peaks in early-mid S phase, prior to its known Cdk1-mediated phosphorylation, and the two modifications act antagonistically, suggesting that the opposite roles of Cdc13 in telomerase regulation can be separated temporally and regulated by distinct modifications.

Original languageEnglish (US)
Pages (from-to)920-926
Number of pages7
JournalNature Structural and Molecular Biology
Volume18
Issue number8
DOIs
StatePublished - Aug 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

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