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Nat Commun. 2014 Nov 12;5:5312. doi: 10.1038/ncomms6312.

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

Author information

1
Department of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
2
1] Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan [2] Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan.
3
1] Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan [2] Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.

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.

PMID:
25387524
DOI:
10.1038/ncomms6312
[Indexed for MEDLINE]

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