DNA Topoisomerase II Poisons and the Cell Cycle
Nuclear DNA, a target for many anticancer drugs, does not exist inside a human cell as an extended, relaxed and unrestrained molecule. Rather, in its protein-associated form of chromatin it is highly organized with order being imposed by specific DNA-protein interactions. The imposition of such restraints on the free movement of DNA molecules within the nucleus means that any topological problems must be actively resolved by the topoisomerase enzymes (1). The major type II enzyme, DNA topoisomerase II, is strategically located at the base of chromatin loop domains to carry out its housekeeping functions and operates by forming temporary gates in double stranded DNA (Fig. 1) through which an intact helix can pass. Several classes of antitumor drugs are now recognized as topoisomerase poisons because of their ability to trap the enzyme gates on DNA in the form of stabilized cleavable complexes (Fig. 1).
KeywordsSmall Cell Lung Cancer Cell Intercalate Agent Cleavable Complex Cell Cycle Delay Cell Cycle Perturbation
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