Cisplatin DNA cross-links do not inhibit S-phase and cause only a G2/M arrest in Saccharomyces cerevisiae.
Cisplatin (CDDP) has been used as a DNA cross-linking agent to evaluate whether there is a specific cell cycle checkpoint response to such damage in Saccharomyces cerevisiae (S. cerevisiae). Fluorescent-activated cell sorting (FACS) analysis showed only a G2/M checkpoint, normal exit from G1 and progression through S-phase following alpha-factor arrest and CDDP treatment. Of the checkpoint mutants tested, rad9, rad17 and rad24, did not show increased sensitivity to CDDP compared to isogenic wild-type cells. However, other checkpoint mutants tested (mec1, mec3 and rad53) showed increased sensitivity to CDDP, as did controls with a defect in excision repair (rad1 and rad14) or a defect in recombination (rad51 and rad52). Thus, by survival and cell cycle kinetics, it appears that DNA cross-links do not inhibit entry into S-phase or slow DNA replication and that replication continues after cisplatin treatment in yeast.
Grossmann
K F
KF
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201, USA.
Brown
J C
JC
Moses
R E
RE
D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D018797:Cell Cycle Proteins; D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes; D004271:DNA, Fungal / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004720:Endonucleases / Q000235:genetics; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000235:genetics; D016195:G2 Phase / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008938:Mitosis / Q000187:drug effects; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D016196:S Phase / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C072975:RAD14 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C104169:DUN1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D004720:Endonucleases; C069266:RAD1 protein, S cerevisiae; D045643:DNA Repair Enzymes; D002945:Cisplatin