Saccharomyces cerevisiae lacking Snm1, Rev3 or Rad51 have a normal S-phase but arrest permanently in G2 after cisplatin treatment.
The role of Snm1, Rev3 and Rad51 in S-phase after cisplatin (CDDP) DNA treatment has been examined. When isogenic deletion mutants snm1 delta, rev3 delta and rad51 delta were arrested in G1 and treated with doses of CDDP causing significant lethality (<20% survival in the mutant strains), they progressed through S-phase with normal kinetics. The mutants arrested in G2 like wild-type cells, however they did not exit the arrest and reenter the cell cycle. This finding demonstrates that these genes are not required to allow DNA replication in the presence of damage. Therefore, Snm1, Rev3 and Rad51 may act after S to allow repair. At high levels of damage (<40% survival in wild-type cells) S-phase was slowed in a MEC1-dependent fashion. The cross-link incision kinetics of snm1 delta and rev3 delta mutants were also examined; both showed no deficiencies in incision of cross-linked DNA.
Grossmann
K F
KF
Department of Molecular and Medical Genetics, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Mail Code: L103, Portland, OR 97201, USA.
Ward
A M
AM
Moses
R E
RE
D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase; D004706:Endodeoxyribonucleases; D005656:Fungal Proteins / Q000235:genetics*; D011564:Furocoumarins / Q000494:pharmacology; D016195:G2 Phase / Q000235:genetics; D017353:Gene Deletion; D007399:Interphase / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D051135:Rad51 Recombinase; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011564:Furocoumarins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D004259:DNA-Directed DNA Polymerase; C092602:REV3 protein, S cerevisiae; D004706:Endodeoxyribonucleases; C090162:PSO2 protein, S cerevisiae; D002945:Cisplatin