Pif1p helicase, a catalytic inhibitor of telomerase in yeast

Science. 2000 Aug 4;289(5480):771-4. doi: 10.1126/science.289.5480.771.

Abstract

Mutations in the yeast Saccharomyces cerevisiae PIF1 gene, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Motifs
  • Animals
  • Catalysis
  • Cell Line
  • Chromosomes, Fungal / metabolism
  • DNA Damage
  • DNA Helicases / chemistry
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Replication
  • DNA, Fungal / metabolism
  • Gene Expression
  • Humans
  • Mutagenesis, Site-Directed
  • Point Mutation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Recombination, Genetic
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Telomerase / antagonists & inhibitors*
  • Telomerase / metabolism
  • Telomere / metabolism*

Substances

  • DNA, Fungal
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Telomerase
  • PIF1 protein, S cerevisiae
  • DNA Helicases