Shen, Zih-JieZih-JieShenHsu, Pang-HungPang-HungHsuSu, Yu-TaiYu-TaiSuYang, Chia-WeiChia-WeiYangKao, LiLiKaoTseng, Shun-FuShun-FuTsengTsai, Ming-DawMing-DawTsaiTeng, Shu-ChunShu-ChunTeng2024-07-172024-07-172014-11-12https://scholars.lib.ntu.edu.tw/handle/123456789/719865In yeast, the initiation of telomere replication at the late S phase involves in combined actions of kinases on Cdc13, the telomere binding protein. Cdc13 recruits telomerase to telomeres through its interaction with Est1, a component of telomerase. However, how cells terminate the function of telomerase at G2/M is still elusive. Here we show that the protein phosphatase 2A (PP2A) subunit Pph22 and the yeast Aurora kinase homologue Ipl1 coordinately inhibit telomerase at G2/M by dephosphorylating and phosphorylating the telomerase recruitment domain of Cdc13, respectively. While Pph22 removes Tel1/Mec1-mediated Cdc13 phosphorylation to reduce Cdc13-Est1 interaction, Ipl1-dependent Cdc13 phosphorylation elicits dissociation of Est1-TLC1, the template RNA component of telomerase. Failure of these regulations prevents telomerase from departing telomeres, causing perturbed telomere lengthening and prolonged M phase. Together our results demonstrate that differential and additive actions of PP2A and Aurora on Cdc13 limit telomerase action by removing active telomerase from telomeres at G2/M phase.enjournal article10.1038/ncomms631225387524