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PMID:10926538
| Citation |
Zhou, J, Monson, EK, Teng, SC, Schulz, VP and Zakian, VA (2000) Pif1p helicase, a catalytic inhibitor of telomerase in yeast. Science 289:771-4 |
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| 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. |
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| Keywords |
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 |
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