A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres
Jonathan Strecker,
Sonia Stinus,
Mariana Pliego Caballero,
Rachel K Szilard,
Michael Chang,
Daniel Durocher
Affiliations
Jonathan Strecker
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada
Sonia Stinus
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Mariana Pliego Caballero
European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Rachel K Szilard
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada
DNA double-strand breaks (DSBs) and short telomeres are structurally similar, yet they have diametrically opposed fates. Cells must repair DSBs while blocking the action of telomerase on these ends. Short telomeres must avoid recognition by the DNA damage response while promoting telomerase recruitment. In Saccharomyces cerevisiae, the Pif1 helicase, a telomerase inhibitor, lies at the interface of these end-fate decisions. Using Pif1 as a sensor, we uncover a transition point in which 34 bp of telomeric (TG1-3)n repeat sequence renders a DNA end insensitive to Pif1 action, thereby enabling extension by telomerase. A similar transition point exists at natural chromosome ends, where telomeres shorter than ~40 bp are inefficiently extended by telomerase. This phenomenon is not due to known Pif1 modifications and we instead propose that Cdc13 renders TG34+ ends insensitive to Pif1 action. We contend that the observed threshold of Pif1 activity defines a dividing line between DSBs and telomeres.
