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.
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We thank S. Li (Duke–National University of Singapore Graduate Medical School) and E. Blackburn (University of California, San Francisco) for the Phos-Thr308 antibody and for several strains, as well as acknowledge S. Li's kind help in using these reagents. We thank M. Lei and S. Gasser for sharing unpublished results; M. Arneric, B. Luke, M. Hohl and A. Chan for helping to set up the G-overhang and telomere measurement experiments; Zhao lab members, particularly C. Cremona and P. Sarangi, and N. Lue and T. Weinert for comments on the manuscript; as well as V.A. Zakian, in whose lab some of this work was carried out, for discussions on experiments and comments on the manuscript. This work was supported by US National Institutes of Health (NIH) grant R01GM080670 and Bressler Scholars Award (to X.Z.), a fellowship from the Canadian Institutes of Health Research (to I. C.) and NIH grant GM43265 to V.A. Zakian.
The authors declare no competing financial interests.
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Hang, L., Liu, X., Cheung, I. et al. SUMOylation regulates telomere length homeostasis by targeting Cdc13. Nat Struct Mol Biol 18, 920–926 (2011). https://doi.org/10.1038/nsmb.2100
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