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S. cerevisiae has three pathways for DNA interstrand crosslink repair.

Yeast mutants, snm1 (pso2-1), rev3 (pso1-1), and rad51, which display significant sensitivity to interstrand crosslinks (ICLs) have low relative sensitivity to other DNA damaging agents. SNM1, REV3, and RAD51 were disrupted in the same haploid strain, singly and in combination. The double mutants, snm1 Delta rev3 Delta, snm1 Delta rad51 Delta and rev3 Delta rad51 Delta were all more sensitive to ICLs than any of the single mutants, indicating that they are in separate epistasis groups for survival. A triple mutant displayed greater sensitivity to ICLs than any of the double mutants, with one ICL per genome being lethal. Therefore, Saccharomyces cerevisiae appears to have three separate ICL repair pathways, but no more. S-phase delay was not observed after ICL damage introduced by cisplatin (CDDP) or 8-methoxypsoralen (8-MOP) during the G1-phase, in any of the above mutants, or in an isogenic rad14 Delta mutant deficient in nucleotide excision repair. However, the psoralen analog angelicin (monoadduct damage) induced a significant S-phase delay in the rad14 Delta mutant. Thus, normal S-phase in the presence of ICLs does not seem to be due to rapid excision repair. The results also indicate that monoadduct formation by CDDP or 8-MOP at the doses used is not sufficient to delay S-phase in the rad14 Delta mutant. While the sensitivity of a rev3 Delta mutant indicates Pol zeta is needed for optimal ICL repair, isogenic cells deficient in Pol eta (rad30 Delta cells) were not significantly more sensitive to ICL agents than wild-type cells, and have no S-phase delay.

Pubmed ID: 11738934

Authors

  • Grossmann KF
  • Ward AM
  • Matkovic ME
  • Folias AE
  • Moses RE

Journal

Mutation research

Publication Data

December 19, 2001

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM58186

Mesh Terms

  • Cisplatin
  • Cross-Linking Reagents
  • DNA Damage
  • DNA Repair
  • DNA, Fungal
  • DNA-Binding Proteins
  • DNA-Directed DNA Polymerase
  • Endodeoxyribonucleases
  • Epistasis, Genetic
  • Fungal Proteins
  • Furocoumarins
  • Methoxsalen
  • Nuclear Proteins
  • Rad51 Recombinase
  • S Phase
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins