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 indu ced by UV radiation. Here we demonstrate that in the yeast Saccharomyc es 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 (MN NG). Surprisingly, mutations in photolyase were associated with resist ance of yeast cells to cis-DDP, MNNG, 4-nitroquinoline oxide (4NQO), a nd HN2. Transformation of yeast photolyase mutants with the photolyase gene increased sensitivity to these agents. Thus, while the binding o f photolyase to DNA damaged by UV radiation aids survival of the cell, binding to DNA damaged by other agents may interfere with cell surviv al, perhaps by making the lesions inaccessible to the nucleotide excis ion repair system.