Pif1p helicase, a catalytic inhibitor of telomerase in yeast.
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.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
J
J
Zhou
E K
EK
Monson
S C
SC
Teng
V P
VP
Schulz
V A
VA
Zakian
D000483:Alleles; D020816:Amino Acid Motifs; D000818:Animals; D002384:Catalysis; D002460:Cell Line; D015825:Chromosomes, Fungal / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004271:DNA, Fungal / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D004271:DNA, Fungal; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase; C085463:PIF1 protein, S cerevisiae; D004265:DNA Helicases