Article
Directed evolution to increase camptothecin sensitivity of human DNA topoisomerase I.
Chemistry & biology - 1 Sept 2001
Scaldaferro S, Tinelli S, Borgnetto M E, Azzini A, Capranico G
Abstract excerpt
BACKGROUND: Human DNA topoisomerase I (top1) relaxes DNA supercoiling during basic nuclear processes. The enzyme is the main target of antitumor agents, such as camptothecins (CPT), that transform top1 into a DNA-damaging agent. RESULTS: By directed evolution of a C-terminal portion, we selected human top1 mutants that were 22-28-fold more CPT-sensitive than wild-type top1 in Saccharomyces cerevisiae cells. The...
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