TY - JOUR
T1 - S. cerevisiae has three pathways for DNA interstrand crosslink repair
AU - Grossmann, Kenneth F.
AU - Ward, Alex M.
AU - Matkovic, Mara E.
AU - Folias, Alexandra E.
AU - Moses, Robb E.
N1 - Funding Information:
This research was supported by a grant from the National Institutes of Health, National Institute of General Medical Sciences (GM58186). The authors thank Dr. James Hejna and Dr. Betsy Ferguson for helpful discussions.
PY - 2001/12/19
Y1 - 2001/12/19
N2 - 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, snm1Δ rev3Δ, snm1Δ rad51Δ and rev3Δ rad51Δ 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 rad14Δ mutant deficient in nucleotide excision repair. However, the psoralen analog angelicin (monoadduct damage) induced a significant S-phase delay in the rad14Δ 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 rad14Δ mutant. While the sensitivity of a rev3Δ mutant indicates Polζ is needed for optimal ICL repair, isogenic cells deficient in Polη (rad30Δ cells) were not significantly more sensitive to ICL agents than wild-type cells, and have no S-phase delay.
AB - 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, snm1Δ rev3Δ, snm1Δ rad51Δ and rev3Δ rad51Δ 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 rad14Δ mutant deficient in nucleotide excision repair. However, the psoralen analog angelicin (monoadduct damage) induced a significant S-phase delay in the rad14Δ 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 rad14Δ mutant. While the sensitivity of a rev3Δ mutant indicates Polζ is needed for optimal ICL repair, isogenic cells deficient in Polη (rad30Δ cells) were not significantly more sensitive to ICL agents than wild-type cells, and have no S-phase delay.
KW - Angelicin
KW - Cisplatin
KW - DNA interstrand crosslinks
KW - DNA repair
KW - Psoralen
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U2 - 10.1016/S0921-8777(01)00106-9
DO - 10.1016/S0921-8777(01)00106-9
M3 - Article
C2 - 11738934
AN - SCOPUS:0035915410
SN - 0921-8777
VL - 487
SP - 73
EP - 83
JO - Mutation Research - DNA Repair
JF - Mutation Research - DNA Repair
IS - 3-4
ER -