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PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase

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  • Zih-Jie Shen

    (College of Medicine, National Taiwan University)

  • Pang-Hung Hsu

    (Genomics Research Center, Academia Sinica
    Institute of Bioscience and Biotechnology, National Taiwan Ocean University)

  • Yu-Tai Su

    (College of Medicine, National Taiwan University)

  • Chia-Wei Yang

    (College of Medicine, National Taiwan University)

  • Li Kao

    (College of Medicine, National Taiwan University)

  • Shun-Fu Tseng

    (College of Medicine, National Taiwan University)

  • Ming-Daw Tsai

    (Genomics Research Center, Academia Sinica
    Institute of Biological Chemistry, Academia Sinica)

  • Shu-Chun Teng

    (College of Medicine, National Taiwan University)

Abstract

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.

Suggested Citation

  • Zih-Jie Shen & Pang-Hung Hsu & Yu-Tai Su & Chia-Wei Yang & Li Kao & Shun-Fu Tseng & Ming-Daw Tsai & Shu-Chun Teng, 2014. "PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6312
    DOI: 10.1038/ncomms6312
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