The Saccharomyces cerevisiae RAD9, RAD17 and RAD24 genes are required for suppression of mutagenic post-replicative repair during chronic DNA damage

DNA Repair (Amst). 2010 Jul 1;9(7):824-34. doi: 10.1016/j.dnarep.2010.04.007. Epub 2010 May 15.


In Saccharomyces cerevisiae, a DNA damage checkpoint in the S-phase is responsible for delaying DNA replication in response to genotoxic stress. This pathway is partially regulated by the checkpoint proteins Rad9, Rad17 and Rad24. Here, we describe a novel hypermutable phenotype for rad9Delta, rad17Delta and rad24Delta cells in response to a chronic 0.01% dose of the DNA alkylating agent MMS. We report that this hypermutability results from DNA damage introduction during the S-phase and is dependent on a functional translesion synthesis pathway. In addition, we performed a genetic screen for interactions with rad9Delta that confer sensitivity to 0.01% MMS. We report and quantify 25 genetic interactions with rad9Delta, many of which involve the post-replication repair machinery. From these data, we conclude that defects in S-phase checkpoint regulation lead to increased reliance on mutagenic translesion synthesis, and we describe a novel role for members of the S-phase DNA damage checkpoint in suppressing mutagenic post-replicative repair in response to sublethal MMS treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Cycle Proteins / genetics*
  • DNA Damage*
  • DNA Repair / genetics*
  • DNA Replication
  • DNA-Binding Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Mutagenesis
  • Nuclear Proteins / genetics*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Suppression, Genetic


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • RAD17 protein, S cerevisiae
  • RAD24 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • rad9 protein