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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinases / metabolism
  • Aurora Kinases / physiology*
  • Cell Division / physiology*
  • G2 Phase / physiology*
  • Protein Phosphatase 2 / metabolism
  • Protein Phosphatase 2 / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Telomerase / metabolism
  • Telomerase / physiology*
  • Telomere / metabolism
  • Telomere / physiology*
  • Telomere-Binding Proteins / metabolism
  • Telomere-Binding Proteins / physiology*

Substances

  • Cdc13 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Telomere-Binding Proteins
  • Aurora Kinases
  • IPL1 protein, S cerevisiae
  • Telomerase
  • Pph22 protein, S cerevisiae
  • Protein Phosphatase 2