DNA damage-processing pathways involved in the eukaryotic cellular response to anticancer DNA cross-linking drugs. Molecular pharmacology

We used a panel of isogenic Saccharomyces cerevisiae strains compromised in several different DNA damage-processing pathways to assess in vivo processing of DNA adducts induced by four cross-linking anticancer drugs. By examining cytotox-icity profiles, cell cycle arrest patterns, and determining recom-bination and mutation frequencies, we found that cisplatin-, nitrogen mustard-, mitomycin-, and carmustine-induced DNA adducts in S. cerevisiae are processed by components of the nucleotide excision repair (NER), recombination repair (RR), and translesion synthesis (TLS) pathways, with substantially different contributions of each pathway for the drugs studied here. In contrast to previous studies that used single pathway-compromised strains to identify genes that mediate sensitivity to DNA cross-linking drugs, we used strains that were compro