A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres
- Lunenfeld-Tanenbaum Research Institute, Canada
- University Medical Center Groningen, Netherlands
Abstract
DNA double-strand breaks (DSBs) and short telomeres are structurally similar, yet 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.
Article and author information
Author details
Funding
Canadian Institutes of Health Research
- Jonathan Strecker
- Daniel Durocher
Krembil Foundation
- Daniel Durocher
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Sonia Stinus
- Michael Chang
Canadian Institutes of Health Research (FDN143343)
- Daniel Durocher
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Strecker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres
eLife 6:e23783.
https://doi.org/10.7554/eLife.23783
