A Novel Role for DNA Photolyase: Binding to DNA Damaged by Drugs Is Associated with Enhanced Cytotoxicity in Saccharomyces cerevisiae

Autor: Brian J. Feldman, Gilbert Chu, M E Fox
Rok vydání: 1994
Předmět:
Zdroj: Molecular and Cellular Biology. 14:8071-8077
ISSN: 1098-5549
DOI: 10.1128/mcb.14.12.8071-8077.1994
Popis: 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.
Databáze: OpenAIRE