Deletion of the SRS2 gene suppresses elevated recombination and DNA damage sensitivity in rad5 and rad18 mutants of Saccharomyces cerevisiae

Mutat Res. 2001 Jul 12;486(2):137-46. doi: 10.1016/s0921-8777(01)00086-6.

Abstract

The Saccharomyces cerevisiae genes RAD5, RAD18, and SRS2 are proposed to act in post-replicational repair of DNA damage. We have investigated the genetic interactions between mutations in these genes with respect to cell survival and ectopic gene conversion following treatment of logarithmic and early stationary cells with UV- and gamma-rays. We find that the genetic interaction between the rad5 and rad18 mutations depends on DNA damage type and position in the cell cycle at the time of treatment. Inactivation of SRS2 suppresses damage sensitivity both in rad5 and rad18 mutants, but only when treated in logarithmic phase. When irradiated in stationary phase, the srs2 mutation enhances the sensitivity of rad5 mutants, whereas it has no effect on rad18 mutants. Irrespective of the growth phase, the srs2 mutation reduces the frequency of damage-induced ectopic gene conversion in rad5 and rad18 mutants. In addition, we find that srs2 mutants exhibit reduced spontaneous and UV-induced sister chromatid recombination (SCR), whereas rad5 and rad18 mutants are proficient for SCR. We propose a model in which the Srs2 protein has pro-recombinogenic or anti-recombinogenic activity, depending on the context of the DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine Triphosphatases*
  • DNA Damage / genetics*
  • DNA Helicases / genetics
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • Fungal Proteins / genetics
  • Genes, Fungal*
  • Models, Genetic
  • Radiation, Ionizing
  • Recombination, Genetic / genetics*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / radiation effects
  • Saccharomyces cerevisiae Proteins*

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • RAD18 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • SRS2 protein, S cerevisiae
  • Adenosine Triphosphatases
  • RAD5 protein, S cerevisiae
  • DNA Helicases