DNA polymerase 4 of Saccharomyces cerevisiae is important for accurate repair of methyl-methanesulfonate-induced DNA damage

Genetics. 2006 Jan;172(1):89-98. doi: 10.1534/genetics.105.049254. Epub 2005 Oct 11.

Abstract

The DNA polymerase 4 protein (Pol4) of Saccharomyces cerevisiae is a member of the X family of DNA polymerases whose closest human relative appears to be DNA polymerase lambda. Results from previous genetic studies conflict over the role of Pol4 in vivo. Here we show that deletion of Pol4 in a diploid strain of the SK1 genetic background results in sensitivity to methyl methanesulfonate (MMS). However, deletion of Pol4 in other strain backgrounds and in haploid strains does not yield an observable phenotype. The MMS sensitivity of a Pol4-deficient strain can be rescued by deletion of YKu70. We also show that deletion of Pol4 results in a 6- to 14-fold increase in the MMS-induced mutation frequency and in a significant increase in AT-to-TA transversions. Our studies suggest that Pol4 is critical for accurate repair of DNA lesions induced by MMS.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Nuclear / genetics
  • Base Sequence
  • DNA Damage / drug effects*
  • DNA Polymerase beta
  • DNA Repair / drug effects
  • DNA Repair / genetics*
  • DNA Replication
  • DNA, Fungal / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Directed DNA Polymerase / genetics*
  • DNA-Directed DNA Polymerase / metabolism
  • Ku Autoantigen
  • Methyl Methanesulfonate / toxicity
  • Molecular Sequence Data
  • Mutation / genetics
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Antigens, Nuclear
  • DNA, Fungal
  • DNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Methyl Methanesulfonate
  • DNA Polymerase beta
  • DNA-Directed DNA Polymerase
  • POL4 protein, S cerevisiae
  • Xrcc6 protein, human
  • Ku Autoantigen