RPA facilitates telomerase activity at chromosome ends in budding and fission yeasts

EMBO J. 2012 Apr 18;31(8):2034-46. doi: 10.1038/emboj.2012.40. Epub 2012 Feb 21.

Abstract

In Saccharomyces cerevisiae, the telomerase complex binds to chromosome ends and is activated in late S-phase through a process coupled to the progression of the replication fork. Here, we show that the single-stranded DNA-binding protein RPA (replication protein A) binds to the two daughter telomeres during telomere replication but only its binding to the leading-strand telomere depends on the Mre11/Rad50/Xrs2 (MRX) complex. We further demonstrate that RPA specifically co-precipitates with yKu, Cdc13 and telomerase. The interaction of RPA with telomerase appears to be mediated by both yKu and the telomerase subunit Est1. Moreover, a mutation in Rfa1 that affects both the interaction with yKu and telomerase reduces the dramatic increase in telomere length of a rif1Δ, rif2Δ double mutant. Finally, we show that the RPA/telomerase association and function are conserved in Schizosaccharomyces pombe. Our results indicate that in both yeasts, RPA directly facilitates telomerase activity at chromosome ends.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes / metabolism*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutation, Missense
  • Protein Binding
  • Protein Interaction Mapping
  • Replication Protein A / metabolism*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / growth & development
  • Telomerase / metabolism*
  • Telomere / metabolism*

Substances

  • Mutant Proteins
  • RFA1 protein, S cerevisiae
  • Replication Protein A
  • Saccharomyces cerevisiae Proteins
  • Telomerase