The enzyme telomerase maintains chromosome integrity by synthesizing telomeres at chromosome ends. What prevents telomerase from adding telomeres to double-stranded DNA breaks (DSBs)? In Nature Cell Biology, Svetlana Makovets and Elizabeth Blackburn now report that DNA damage signalling induces phosphorylation of the telomerase inhibitor Pif1 (petite integration frequency 1). Phosphorylation of Pif1 blocks the activity of telomerase at DNA breaks but not at chromosome ends.

In budding yeast, DSBs sustained during normal growth or as a result of genotoxic stress activate the kinases Tel1 and Mec1—orthologues of mammalian ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related), respectively—to induce phosphorylation of the checkpoint kinases Chk1 and Rad53. Makovets and Blackburn found that Pif1, which is known to antagonize telomerase function at DNA ends, is phosphorylated following DNA damage. Deletion of MEC1 or RAD53 blocks DNA damage-induced Pif1 phosphorylation, although Rad53 is not required for the recruitment of Pif1 to DSBs. These data indicate that the DNA damage response pathway regulates Pif1 phosphorylation but not Pif1 localization.