DNA Topoisomerase II Poisons and the Cell Cycle

作者: P. J. Smith

DOI: 10.1007/978-1-4613-1253-6_14

关键词: DNATopoisomeraseHelixChromatin LoopCell cycleNuclear DNAChromatinChemistryEnzymeBiophysics

摘要: Nuclear DNA, a target for many anticancer drugs, does not exist inside 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 such restraints on the free movement DNA molecules within nucleus means that any topological problems must be actively resolved topoisomerase enzymes (1). major type II enzyme, II, strategically located at base loop domains to carry out housekeeping functions operates forming temporary gates double stranded (Fig. 1) through which intact helix can pass. Several classes antitumor drugs are now recognized poisons because their ability trap enzyme stabilized cleavable complexes 1).

参考文章(17)
Bonnie Glisson, Radhey Gupta, Warren Ross, Paula Hodges, Cross-resistance to intercalating agents in an epipodophyllotoxin-resistant Chinese hamster ovary cell line: evidence for a common intracellular target Cancer Research. ,vol. 46, pp. 1939- 1942 ,(1986)
Warren E. Ross, Antoinette J. Wozniak, DNA Damage as a Basis for 4′-Demethylepipodophyllotoxin-9-(4,6-O-ethylidene-β-d-glucopyranoside) (Etoposide) Cytotoxicity Cancer Research. ,vol. 43, pp. 120- 124 ,(1983)
M L Slevin, P I Clark, S P Joel, S Malik, R J Osborne, W M Gregory, D G Lowe, R H Reznek, P F Wrigley, A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer. Journal of Clinical Oncology. ,vol. 7, pp. 1333- 1340 ,(1989) , 10.1200/JCO.1989.7.9.1333
M. M. Heck, W. N. Hittelman, W. C. Earnshaw, Differential expression of DNA topoisomerases I and II during the eukaryotic cell cycle. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 85, pp. 1086- 1090 ,(1988) , 10.1073/PNAS.85.4.1086
Richard J. Epstein, Paul J. Smith, Mitogen-induced topoisomerase II synthesis precedes DNA synthesis in human breast cancer cells Biochemical and Biophysical Research Communications. ,vol. 160, pp. 12- 17 ,(1989) , 10.1016/0006-291X(89)91613-6
Jan Kapuscinski, Zbigniew Darzynkiewicz, Frank Traganos, Myron R. Melamed, Interactions of a new antitumor agent, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]-ethyl]amino]-9,10-anthracenedione, with nucleic acids. Biochemical Pharmacology. ,vol. 30, pp. 231- 240 ,(1981) , 10.1016/0006-2952(81)90083-6