Quinone-induced enhancement of DNA cleavage by human topoisomerase IIalpha: adduction of cysteine residues 392 and 405.

ABSTRACT: Several quinone-based metabolites of drugs and environmental toxins are potent topoisomerase II poisons. These compounds act by adducting the protein and appear to increase levels of enzyme-DNA cleavage complexes by at least two potentially independent mechanisms. Treatment of topoisomerase IIalpha with quinones inhibits DNA religation and blocks the N-terminal gate of the protein by cross-linking its two protomer subunits. It is not known whether these two effects result from adduction of quinone to the same amino acid residue(s) in topoisomerase IIalpha or whether they are mediated by modification of separate residues. Therefore, this study identified amino acid residues in human topoisomerase IIalpha that are modified by quinones and determined their role in the actions of these compoun

SUBMITTER: Bender RP 

PROVIDER: S-EPMC2896225 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature