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

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

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  • 1Marseille Cancer Research Center CRCM, U1068 Inserm, UMR7258 CNRS, Aix-Marseille Univ, Institut Paoli-Calmettes, Marseille, France.

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.

PMID:
22354040
[PubMed - indexed for MEDLINE]
PMCID:
PMC3343328
Free PMC Article
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