Enzyme topoisomerase

Topoisomerase enzymes control and modify the topologic states of DNA. The mechanisms of these enzymes involve DNA cleavage and strand passage through the break, followed by religation of the cleaved DNA. Two main forms of topoisomerase exist. The type... 

Camptosar ) the covalently bound DNA topoisomerase enzyme and interferes with the DNA breakage-resealing process. Early and late diarrhea Additional toxicities Neutropenia, nausea, and vomiting... 

Giles GI, Sharma RP. Topoisomerase enzymes as therapeutic targets for cancer chemotherapy. Med. Chem. 2005 Jul l(4) 383-94. 

The topoisomerases enzymes are essential in prokaryotic and eukaryotic cell visibility. Most quinolones have a characteristic core planar heterocyclic nucleus. 

Other drugs classified as plant alkaloids include etoposide, irinotecan, teniposide, and topotecan (see Table 36 1). These drugs inhibit specific enzymes known as topoisomerase enzymes, which are necessary for DNA replication.11 Inhibition of these enzymes causes a break in both strands of the DNA double helix, which leads to DNA destruction and cell death. Etoposide and teniposide inhibit the topoisomerase I form of this enzyme, and irinotecan and topotecan inhibit the topoisomerase II form of this enzyme. These drugs are therefore used to limit cell division and cancer growth in various types of neoplastic disease (see Table 36-4). 

In addition, benzene metabolites appear to be able to inhibit enzymes involved with DNA replication and repair, specifically the topoisomerase enzymes (Chen and Eastmond 1995). Singh et al. (1994) have studied the prooxidant and antioxidant properties of iron-hydroquinone and iron-1,2,4-ben-... 

Chen and Eastmond (1995) showed that benzene metabolites can adversely affect human topoisomerases, enzymes involved in DNA replication and repair. No effect of any metabolite was seen on human topoisomerase I or for topoisomerase II for hydroquinone, phenol, 2,2 -biphenol, 4,4 -biphenol and catechol at concentrations as high as 500 pM. 1,4-Benzoquinone and 1,2,4-benzenetriol inhibited human topoisomerase II in vitro, at 500 and 250 pM without bioactivation. However, following bioactivation, phenol and 2,2 -biphenol showed inhibitory effects at doses as low as 50 pM, whereas 4,4 -biphenol inhibited topoisomerase II at concentrations of 10 pM. 

Function of topoisomerases Enzymes that assist in formation of superhelices and regulate the breaking and rejoining of DNA chains... 

DNA gyrase A type II topoisomerase enzyme present in bacteria that introduces negative supercoils into the DNA double helix in advance of the replication fork. 

Topoisomerase Enzymes that control the amount of supercoiling in DNA. Type 1 topoisomerases will cleave one strand of DNA to relieve supercoiling, whereas type 11 topoisomerases will cleave both strands of the DNA double helix. 

Nalidixic acid and all its analogs act by selectively inhibiting bacterial DNA synthesis. The actual biochemical target of the quinolones is the enzyme DNA-gyrase, a topoisomerase enzyme found only in procaryotic cells. This accounts for the selective toxicity of these drugs. 

Topoisomerase enzymes (topoisomerases I and II) are enzymes that control the changes in DNA structure by breaking and rejoining the phosphodiester backbone of DNA strand during the normal cell cycles. Topoisomerases have become popular targets for cancer chemotherapy drugs. 

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