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 t he formation rate of new telomeres. Here, we show that Pif1p acts by inhibi ting telomerase rather than telomere-telomere recombination, and this inhib ition requires the helicase activity of Pif1p, Overexpression of enzymatica lly active Pif1p causes telomere shortening. Thus, Pif1p is a catalytic inh ibitor of telomerase-mediated telomere Lengthening, Because Pif1p is associ ated 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 stab ility by suppressing telomerase-mediated healing of double-strand breaks.