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Pif1p Helicase, a Catalytic Inhibitor of Telomerase in Yeast

Science  04 Aug 2000:
Vol. 289, Issue 5480, pp. 771-774
DOI: 10.1126/science.289.5480.771

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Abstract

Mutations in the yeast Saccharomyces cerevisiae PIF1gene, which encodes a 5′-to-3′ DNA helicase, cause telomere lengthening and a large increase in the formation rate of new telomeres. Here, we show that Pif1p acts by inhibiting telomerase rather than telomere-telomere recombination, and this inhibition requires the helicase activity of Pif1p. Overexpression of enzymatically active Pif1p causes telomere shortening. Thus, Pif1p is a catalytic inhibitor of telomerase-mediated telomere lengthening. Because Pif1p is associated with telomeric DNA in vivo, its effects on telomeres are likely direct. Pif1p-like helicases are found in diverse organisms, including humans. We propose that Pif1p-mediated inhibition of telomerase promotes genetic stability by suppressing telomerase-mediated healing of double-strand breaks.

  • * These authors contributed equally to this work.

  • Present address: Genaissance Pharmaceuticals, Five Science Park, New Haven, CT 06511, USA.

  • To whom correspondence should be addressed: E-mail: vzakian{at}molbio.princeton.edu

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