title: SUMOylation regulates telomere length homeostasis by targeting Cdc13.
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.
authors: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors: Lisa E
authors: LE
authors: Hang
authors: Xianpeng
authors: X
authors: Liu
authors: Iris
authors: I
authors: Cheung
authors: Yan
authors: Y
authors: Yang
authors: Xiaolan
authors: X
authors: Zhao
mesh_terms: D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D004843:Epistasis, Genetic; D006706:Homeostasis; D010766:Phosphorylation; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D058207:Sumoylation; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C452219:Cdc13 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; C428109:Stn1 protein, S cerevisiae; D034501:Telomere-Binding Proteins