Pif1p helicase, a catalytic inhibitor of telomerase in yeast.
Publication Year
2000
Type
Journal Article
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.
Keywords
Animals,
Humans,
Catalysis,
Recombinant Proteins,
Cell Line,
Mutagenesis, Site-Directed,
Sequence Homology, Amino Acid,
Gene Expression,
Saccharomyces cerevisiae Proteins,
Saccharomyces cerevisiae,
DNA Replication,
DNA Damage,
Alleles,
Telomere,
Recombination, Genetic,
Amino Acid Motifs,
Point Mutation,
DNA Helicases,
Telomerase,
DNA, Fungal,
Chromosomes, Fungal
Journal
Science
Volume
289
Issue
5480
Pages
771-4
Date Published
08/2000
ISSN Number
0036-8075
Alternate Journal
Science
PMID
10926538