A novel role for DNA photolyase: binding to DNA damaged by drugs is associated with enhanced cytotoxicity in Saccharomyces cerevisiae.
DNA photolyase binds to and repairs cyclobutane pyrimidine dimers induced by UV radiation. Here we demonstrate that in the yeast Saccharomyces cerevisiae, photolyase also binds to DNA damaged by the anticancer drugs cis-diamminedichloroplatinum (cis-DDP) and nitrogen mustard (HN2) and by the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Surprisingly, mutations in photolyase were associated with resistance of yeast cells to cis-DDP, MNNG, 4-nitroquinoline oxide (4NQO), and HN2. Transformation of yeast photolyase mutants with the photolyase gene increased sensitivity to these agents. Thus, while the binding of photolyase to DNA damaged by UV radiation aids survival of the cell, binding to DNA damaged by other agents may interfere with cell survival, perhaps by making the lesions inaccessible to the nucleotide excision repair system.
Department of Medicine, Stanford University School of Medicine, California 94305.
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Fox
B J
BJ
Feldman
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Chu
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D002945:Cisplatin / Q000633:toxicity; D004249:DNA Damage; D004271:DNA, Fungal / Q000187:drug effects*; D004268:DNA-Binding Proteins; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004706:Endodeoxyribonucleases; D005656:Fungal Proteins / Q000502:physiology; D008466:Mechlorethamine / Q000633:toxicity; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D011740:Pyrimidine Dimers; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011740:Pyrimidine Dimers; D029701:Saccharomyces cerevisiae Proteins; C073998:RAD2 protein, S cerevisiae; D008769:Methylnitronitrosoguanidine; D008466:Mechlorethamine; D015112:4-Nitroquinoline-1-oxide; D004706:Endodeoxyribonucleases; D004255:Deoxyribodipyrimidine Photo-Lyase; D002945:Cisplatin