Telomerase regulation by the Pif1 helicase: a length-dependent effect?

Dysfunctional telomere length regulation is detrimental to human health, and both activation and inhibition of telomerase have been proposed in potential therapies to treat human diseases. The Saccharomyces cerevisiae Pif1 protein is an evolutionarily conserved helicase that inhibits telomerase activity at DNA ends. Recent studies have indicated that Pif1 is specifically important for inhibiting telomerase at DNA ends with very little or no telomeric sequence and at long telomeres. At the former, Pif1 prevents the inappropriate addition of a telomere at DNA double-strand breaks. For the latter, Pif1 has been shown to bind long telomeres to presumably promote the extension of the short ones. These observations leave the impression that Pif1 does not act at DNA ends with telomeric sequence of intermediate length. Here, we provide in vivo evidence that Pif1 inhibits telomerase activity at DNA ends regardless of telomere sequence length.