The HMG-domain protein Ixr1 blocks excision repair of cisplatin-DNA adducts in yeast.

摘要: Ixr1 is a yeast HMG-domain protein which binds the major DNA adducts of antitumor drug cisplatin. Previous work demonstrated that Saccharomyces cerevisiae cells lacking IXR1 gene were two-fold less sensitive to cisplatin treatment than wild-type cells, and present investigation reveals six-fold difference in having different background. The possibility lower cytotoxicity ixrl strain result enhanced repair was investigated rad1, rad2, rad4, rad6, rad9, rad10, rad14 rad52 backgrounds. In three excision mutants, rad4 rad14, differential sensitivity caused by removing nearly abolished. This demonstrates greater resistance most likely consequence repair, supporting theory other proteins can block cisplatin-DNA vivo. those persisted rad1 rad10 strains, however, indicating these two act at stage pathway where damage recognition critical. A model proposed account for results, strongly supported recently identified functional roles rad products. mutant more RAD52 parental strain, Rad52, double-strand break protein, repairs adducts, probably interstrand cross-links. consistent with not blocking removed rad6 strains behaved similarly, except they both substantially Interruption RAD9 gene, involved DNA-damage-induced cell cycle arrest, had no affect on cytotoxicity.