1. Chromosomes and Gene Expression

A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres

  1. Jonathan Strecker
  2. Sonia Stinus
  3. Mariana Pliego Caballero
  4. Rachel K Szilard
  5. Michael Chang  Is a corresponding author
  6. Daniel Durocher  Is a corresponding author
  1. Lunenfeld-Tanenbaum Research Institute, Canada
  2. University Medical Center Groningen, Netherlands
https://doi.org/10.7554/eLife.23783
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  1. Jonathan Strecker
  2. Sonia Stinus
  3. Mariana Pliego Caballero
  4. Rachel K Szilard
  5. Michael Chang
  6. Daniel Durocher
(2017)
A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres
eLife 6:e23783.
https://doi.org/10.7554/eLife.23783
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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

  1. Jonathan Strecker

    Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.

  2. Sonia Stinus

    European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  3. Mariana Pliego Caballero

    European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  4. Rachel K Szilard

    Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.

  5. Michael Chang

    European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, Netherlands
    For correspondence
    m.chang@umcg.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1706-3337

  6. Daniel Durocher

    Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
    For correspondence
    durocher@lunenfeld.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3863-8635

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.

Reviewing Editor

  1. Kathleen Collins, University of California, Berkeley, United States

Version history

  1. Received: November 30, 2016
  2. Accepted: July 26, 2017
  3. Accepted Manuscript published: August 3, 2017 (version 1)
  4. Version of Record published: September 12, 2017 (version 2)

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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  1. Jonathan Strecker
  2. Sonia Stinus
  3. Mariana Pliego Caballero
  4. Rachel K Szilard
  5. Michael Chang
  6. Daniel Durocher
(2017)
A sharp Pif1-dependent threshold separates DNA double-strand breaks from critically short telomeres
eLife 6:e23783.
https://doi.org/10.7554/eLife.23783

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