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Journals Genetics Volume 189 Issue 4

We have used a novel method to activate the DNA damage S-phase checkpoint response in Saccharomyces cerevisiae to slow lagging-strand DNA replication by exposing cells expressing a drug-sensitive DNA polymerase δ (L612M-DNA pol δ) to the inhibitory drug phosphonoacetic acid (PAA). PAA-treated pol3 -L612M cells arrest as large-budded cells with a single nucleus in the bud neck. This arrest requires all of the components of the S-phase DNA damage checkpoint: Mec1 , Rad9 , the DNA damage clamp Ddc1 - Rad17 - Mec3 , and the Rad24 -dependent clamp loader, but does not depend on Mrc1 , which acts as the signaling adapter for the replication checkpoint. In addition to the above components, a fully functional mismatch repair system, including Exo1 , is required to activate the S-phase damage checkpoint and for cells to survive drug exposure. We propose that mismatch repair activity produces persisting single-stranded DNA gaps in PAA-treated pol3 -L612M cells that are required to increase DNA damage above the threshold needed for checkpoint activation. Our studies have important implications for understanding how cells avoid inappropriate checkpoint activation because of normal discontinuities in lagging-strand replication and identify a role for mismatch repair in checkpoint activation that is needed to maintain genome integrity. Received July 21, 2011. Accepted September 6, 2011. Copyright © 2011 by the Genetics Society of America « Previous | Next Article » Table of Contents This Article Published online before print September 16, 2011 , doi: 10.1534/genetics.111.131938 Genetics December 1, 2011 vol. 189 no. 4 1211-1224 » Abstract Full Text Full Text (PDF) Supporting Information Classifications Investigations Genome Integrity and Transmission Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Reha-Krantz, L. J. PubMed PubMed citation Articles by Reha-Krantz, L. J. Related Content Load related web page information This Months's Issue January 2012, 190 (1) Alert me to new issues of Genetics ABOUT SUBSCRIBE INFO FOR AUTHORS ONLINE SUBMISSION EDITORIAL BOARD CONTACT ALERTS HELP ADVERTISING RSS Help Contact Us International Access Link Print ISSN: 0016-6731 Online ISSN: 1943-2631 Copyright © 2012 by the Genetics Society of America phone: 412-268-1812 fax: 412-268-1813 email: genetics-gsa@andrew.cmu.edu

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Drug-Sensitive DNA Polymerase δ Reveals a Role for Mismatch Repair in Checkpoint Activation in Yeast

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  • Publisher Genetics Society of America
  • Copyright Copyright © 2011 by the Genetics Society of America
  • ISSN 0016-6731
  • eISSN 1943-2631
  • D.O.I. 10.1534/genetics.111.131938
  • Publisher site Get PDF  

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