Cisplatin DNA cross-links do not inhibit S-phase and cause only a G2/M arrest in Saccharomyces cerevisiae

Mutat Res. 1999 May 14;434(1):29-39. doi: 10.1016/s0921-8777(99)00011-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle / drug effects*
  • Cell Cycle / genetics
  • Cell Cycle Proteins*
  • Cisplatin / pharmacology*
  • Cross-Linking Reagents / pharmacology*
  • DNA Damage
  • DNA Repair / genetics
  • DNA Repair Enzymes
  • DNA, Fungal / drug effects*
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism
  • DNA-Binding Proteins*
  • Endonucleases / genetics
  • Flow Cytometry
  • Fungal Proteins / genetics
  • G2 Phase / drug effects
  • Gene Expression Regulation, Fungal / drug effects
  • Genes, Fungal / genetics
  • Microbial Sensitivity Tests
  • Mitosis / drug effects
  • Mutation
  • Protein Kinases / genetics
  • Protein Serine-Threonine Kinases
  • S Phase / drug effects
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*

Substances

  • Cell Cycle Proteins
  • Cross-Linking Reagents
  • DNA, Fungal
  • DNA-Binding Proteins
  • Fungal Proteins
  • RAD14 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • DUN1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Endonucleases
  • RAD1 protein, S cerevisiae
  • DNA Repair Enzymes
  • Cisplatin