PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase.
In 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.
Department of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Zih-Jie
ZJ
Shen
1] Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan [2] Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan.
Pang-Hung
PH
Hsu
Department of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Yu-Tai
YT
Su
Department of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Chia-Wei
CW
Yang
Department of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Li
L
Kao
Department of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Shun-Fu
SF
Tseng
1] Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan [2] Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
Ming-Daw
MD
Tsai
Department of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Shu-Chun
SC
Teng
D064127:Aurora Kinases / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D016195:G2 Phase / Q000502:physiology*; D054648:Protein Phosphatase 2 / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D019098:Telomerase / Q000378:metabolism / Q000502:physiology*; D016615:Telomere / Q000378:metabolism / Q000502:physiology*; D034501:Telomere-Binding Proteins / Q000378:metabolism / Q000502:physiology*
C452219:Cdc13 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D034501:Telomere-Binding Proteins; D064127:Aurora Kinases; C576961:IPL1 protein, S cerevisiae; D019098:Telomerase; C465217:Pph22 protein, S cerevisiae; D054648:Protein Phosphatase 2