Article
Mutation P732L in human DNA topoisomerase IIbeta abolishes DNA cleavage in the presence of calcium and confers drug resistance.
Molecular pharmacology - 1 Jan 2006
Leontiou Chrysoula, Lakey Jeremy H, Lightowlers Robert, Turnbull Rozalind M, Austin Caroline A
Abstract excerpt
The anti cancer drug methyl N-(4'-(9-acridinylamino)-3-methoxy-phenyl) methane sulfonamide (mAMSA) targets human DNA topoisomerase IIbeta. We report here the first selection with mAMSA of resistant human topoisomerase IIbeta. Random mutagenesis of human DNA topoisomerase IIbeta cDNA, followed by selection in yeast for resistance to mAMSA, identified betaP732L. This mutant was 10-fold less sensitive to mAMSA and...
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