Topoisomerase I Poisons and Apoptotic Topoisomerase I-DNA Complexes

Abstract

Topoisomerase I (Top1), an abundant nuclear enzyme expressed throughout the cell cycle, relaxes DNA supercoiling by forming transient covalent DNA cleavage complexes. We will review three situations leading to enhanced cellular Top1 cleavage complexes. First, Top1 cleavage complexes can be stabilized by camptothecins, which are referred to as Top1 poisons and among the most efficient inducers of apoptosis. The second mechanism is related to exogenous and endogenous DNA lesions that enhance Top1 cleavage complexes. Lastly, Top1 cleavage complexes form during programmed cell death and are then referred to as “apoptotic Top1 cleavage complexes.”