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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Cycle / drug effects*
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Cell Cycle / genetics
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Cell Cycle Proteins*
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Cisplatin / pharmacology*
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Cross-Linking Reagents / pharmacology*
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DNA Damage
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DNA Repair / genetics
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DNA Repair Enzymes
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DNA, Fungal / drug effects*
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DNA, Fungal / genetics
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DNA, Fungal / metabolism
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DNA-Binding Proteins*
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Endonucleases / genetics
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Flow Cytometry
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Fungal Proteins / genetics
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G2 Phase / drug effects
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Gene Expression Regulation, Fungal / drug effects
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Genes, Fungal / genetics
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Microbial Sensitivity Tests
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Mitosis / drug effects
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Mutation
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Protein Kinases / genetics
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Protein Serine-Threonine Kinases
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S Phase / drug effects
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Saccharomyces cerevisiae / drug effects*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
Substances
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Cell Cycle Proteins
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Cross-Linking Reagents
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DNA, Fungal
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DNA-Binding Proteins
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Fungal Proteins
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RAD14 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Protein Kinases
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DUN1 protein, S cerevisiae
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Protein Serine-Threonine Kinases
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Endonucleases
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RAD1 protein, S cerevisiae
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DNA Repair Enzymes
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Cisplatin