S. cerevisiae has three pathways for DNA interstrand crosslink repair

Kenneth F. Grossmann, Alex M. Ward, Mara E. Matkovic, Alexandra E. Folias, Robb Moses

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)73-83
Number of pages11
JournalMutation Research - DNA Repair
Volume487
Issue number3-4
DOIs
StatePublished - Dec 19 2001

Fingerprint

S Phase
Saccharomyces cerevisiae
Repair
Methoxsalen
DNA
Yeast
DNA Repair
Ficusin
Cisplatin
Haploidy
G1 Phase
Nucleotides
Genes
Yeasts
Genome

Keywords

  • Angelicin
  • Cisplatin
  • DNA interstrand crosslinks
  • DNA repair
  • Psoralen

ASJC Scopus subject areas

  • Toxicology
  • Genetics
  • Molecular Biology

Cite this

S. cerevisiae has three pathways for DNA interstrand crosslink repair. / Grossmann, Kenneth F.; Ward, Alex M.; Matkovic, Mara E.; Folias, Alexandra E.; Moses, Robb.

In: Mutation Research - DNA Repair, Vol. 487, No. 3-4, 19.12.2001, p. 73-83.

Research output: Contribution to journalArticle

Grossmann, Kenneth F. ; Ward, Alex M. ; Matkovic, Mara E. ; Folias, Alexandra E. ; Moses, Robb. / S. cerevisiae has three pathways for DNA interstrand crosslink repair. In: Mutation Research - DNA Repair. 2001 ; Vol. 487, No. 3-4. pp. 73-83.
@article{be790fb9a421403bbe75beefeb466aa1,
title = "S. cerevisiae has three pathways for DNA interstrand crosslink repair",
abstract = "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.",
keywords = "Angelicin, Cisplatin, DNA interstrand crosslinks, DNA repair, Psoralen",
author = "Grossmann, {Kenneth F.} and Ward, {Alex M.} and Matkovic, {Mara E.} and Folias, {Alexandra E.} and Robb Moses",
year = "2001",
month = "12",
day = "19",
doi = "10.1016/S0921-8777(01)00106-9",
language = "English (US)",
volume = "487",
pages = "73--83",
journal = "Mutation Research - DNA Repair",
issn = "0921-8777",
publisher = "Elsevier BV",
number = "3-4",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=0035915410&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035915410&partnerID=8YFLogxK

U2 - 10.1016/S0921-8777(01)00106-9

DO - 10.1016/S0921-8777(01)00106-9

M3 - Article

C2 - 11738934

AN - SCOPUS:0035915410

VL - 487

SP - 73

EP - 83

JO - Mutation Research - DNA Repair

JF - Mutation Research - DNA Repair

SN - 0921-8777

IS - 3-4

ER -