DNA topoisomerase type

As the two strands of the double helix are separated, positive supercoils are produced in the region of DNA ahead of the replication fork. These interfere with further unwinding of the double helix. DNA topoisomerases Types I and II remove supercoils. Human topoiso-merase II is targeted by anticancer agents, such as etoposide, and DNA gyrase (a Type II topoisomerase found in E. coli that can introduce negative supercoils) is targeted by the antimicrobial quinolones. 

Hirabayashi, S. 1999. Immunohistochemical detection of DNA topoisomerase type II a and Ki-67 in adenoid cystic carcinoma and pleomorphic adenoma of the salivary gland. 7. Oral Pathol. Med. 25 131—136. 

A4 31 DNA topoisomerase type II Carboxylic adds Oxolinic acid Bactericide... 

I topoisomerase of mammals is a 100 kD monomeric protein whose activity is ATP-independent. This enzyme binds to double-stranded DNA and cleaves one of the DNA strands of the duplex, simultaneously forming an enzyme-DNA covalent bond between a tyrosine residue and the 3 -phosphate of the cleaved DNA. The type II topoisomerases are dimeric enzymes, which are ATP-dependant. Two isoforms of topoisomerase II exist, topoisomerase a and (3, with apparent molecular weights of 170 and 180 kD. Topoisomerase... 

Figure 36-18. Comparison of two types of nick-sealing reactions on DNA. The series of reactions at left is catalyzed by DNA topoisomerase I, that at right by DNA ligase P = phosphate, R = ribose, A = ademine. (Slightly modified and reproduced, with permission, from Lehninger AL Biochemistry, 2nd ed. Worth, 1975.)...

Wada S, Reiko T, Akira I, Shunyo M. In vitro inhibitory effects of DNA topoisomerase II by femane-type triterpenoids isolated from a Euphorbia genus. Bioorg Med Chem Lett 1998 8 2829-2832. 

DNAs that differ only in linking number are called topoisomers. Enzymes that underwind and/or relax DNA, the topoisomerases, catalyze changes in linking number. The two classes of topoisomerases, type I and type II, change Lk in increments of 1 or 2, respectively, per catalytic event. 

Berger, J.M. (1998) Type II DNA topoisomerases. Curr. Opin. Struct. Biol. 8, 26-32. 

Correct answer = C. Fluoroquinolones, such as ciprofloxacin, inhibit bacterial DNA gyrase—a type II DNA topoisomerase. This enzyme catalyzes the transient breaking and rejoining of the phosphodiester bonds of the DNA backbone, to allow the removal of positive supercoils during DNA replication. The other enzyme activities mentioned are not affected. Primase synthesizes RNA primers, helicase breaks hydrogen bonds in front of the replication fork, DNA polymerase I removes RNA primers, and DNA igase joins Okazaki fragments. 

WM Huang. Bacterial diversity based on type II DNA topoisomerase genes. Annu Rev Genet 30 79-107, 1996. 

Type II DNA topoisomerase prevents positive supercoiling by introducing negative supercoils at the expense of ATP. 

The indolocarbazole alkaloids and the biosynthetically related bisindolylmaleiraides constitute an important class of natural products, which have been isolated from actinomycetes, cyanobacteria, slime molds, and marine invertebrates [1-3], They display a wide range of biological activities, including antibacterial, antifungal, antiviral, hypotensive, antitumor, and/or neuroprotective properties. The antitumor and neuroprotective activities of indolocarbazoles are the result of one, or several, of the following mechanisms (a) inhibition of different protein kinases, (b) inhibition of DNA topoisomerases, or (c) direct DNA intercalation [3-6], Hundreds of indolocarbazole derivatives have been produced by chemical synthesis or semisynthesis [1,2,6], and several of them have entered clinical trials for the treatment of diverse types of cancer, Parkinson s disease or diabetic retinopathy [3,7]. 

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