DNA helicases Sgs1 and BLM promote DNA double-strand break resection

  1. Serge Gravel,
  2. J. Ross Chapman,
  3. Christine Magill, and
  4. Stephen P. Jackson1
  1. The Wellcome Trust and Cancer Research UK Gurdon Institute, and the Department of Zoology, University of Cambridge, Cambridge CB2 1QN, United Kingdom

Abstract

A key cellular response to DNA double-strand breaks (DSBs) is 5′-to-3′ DSB resection by nucleases to generate regions of ssDNA that then trigger cell cycle checkpoint signaling and DSB repair by homologous recombination (HR). Here, we reveal that in the absence of exonuclease Exo1 activity, deletion or mutation of the Saccharomyces cerevisiae RecQ-family helicase, Sgs1, causes pronounced hypersensitivity to DSB-inducing agents. Moreover, we establish that this reflects severely compromised DSB resection, deficient DNA damage signaling, and strongly impaired HR-mediated repair. Furthermore, we show that the mammalian Sgs1 ortholog, BLM—whose deficiency causes cancer predisposition and infertility in people—also functions in parallel with Exo1 to promote DSB resection, DSB signaling and resistance to DSB-generating agents. Collectively, these data establish evolutionarily conserved roles for the BLM and Sgs1 helicases in DSB processing, signaling, and repair.

Keywords

Footnotes

  • 1 Corresponding author.

    1 E-MAIL s.jackson{at}gurdon.cam.ac.uk; FAX 44-0-1223-334089.

  • Supplemental material is available at http://www.genesdev.org.

  • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.503108.

    • Received August 15, 2008.
    • Accepted August 27, 2008.
  • Freely available online through the Genes & Development Open Access option.

Related Article

| Table of Contents
OPEN ACCESS ARTICLE

Life Science Alliance