From DNA damage to G2 arrest: the many roles of topoisomerase II.
DNA topoisomerase II inhibitors are among the most widely used anticancer agents. These drugs are potent inducers of DNA strand breaks and G2 arrest. However, topoisomerase II is not only a target for anti-cancer drugs but also part of the cellular response to different types of DNA damage. Topoisomerase II forms molecular complexes with important cell cycle regulators including the p53 oncogene suppressor, the BRCT-containing protein TopBP1, 14-3-3 epsilon and Cdc2 kinase. The association between topoisomerase II and Cdc2 kinase likely represents the earliest step in mitotic chromatin condensation. Therefore, regulation of the topoisomerase II/Cdc2 interaction could represent a novel mechanism to delay mitotic onset.
Laboratory of Biology and Pharmacogenetics of Human Tumors, CNRS UMR 8532, Ecole Normale Supérieure, Cachan and Institut Gustave-Roussy, Villejuif 94805, France.
Annette K
AK
Larsen
Alexandre E
AE
Escargueil
Andrzej
A
Skladanowski
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II