DNA topoisomerase I and

Huang X, Okafuji M, Traganos F, Luther E, Holden E, Darzynkiewicz Z. Assessment of histone H2AX phosphorylation induced by DNA topoisomerase I and II inhibitors topotecan and mitoxantrone and by the DNA cross-linking agent cisplatin. Cytometry A. 2004 Apr 58(2) 99-110. 

Kurose A, Tanaka T, Huang X, Halicka HD, Traganos F, Dai W, Darzynkiewicz Z (2005) Assessment of ATM phosphorylation on Ser-1981 induced by DNA topoisomerase I and II inhibitors in relation to Ser-139-histone H2AX phosphorylation, cell cycle phase, apoptosis. Cytometry A 68(1) 1—9... 

Saavedra, R.A. and Huberman, J.A. (1986) Both DNA topoisomerases I and II relax 2 micron plasmid DNA in living yeast cells. Cell 45, 65-70. 

Solary E, Bertrand R, Kohn KW, Pommier Y (1993) Differential induction of apoptosis in imdifferentiated and differentiated HL-60 cells by DNA topoisomerase I and II inhibitors. Blood 81 1359-1368... 

In addition, three enzymes involved in DNA replication, including DNA primases, prokaryotic DNA topoisomerase I and some hexameric DNA helicases, are also classic zinc-ribbon proteins. In bacteriophage DNA primases, mutations of the zinc-binding residues abrogate the synthesis of RNA primers for lagging strand DNA synthesis. Strikingly, each subunit of the mini-chromosomal maintenance (MCM) protein, a heterohexameric helicase that initiates DNA replication in S. cerevisiae, contains an independently folded zinc-ribbon domain that appears to stabilize the dodecameric structure (a dimer of hexamers) of this replication complex. ... 

Anthracydines have several modes of action leading to anticancer activity. They intercalate between base pairs in DNA, interfering with nucleic acid synthesis. Anthracydines also inhibit DNA topoisomerases I and II, which leads to DNA double-strand breaks. In addition, doxorubicin and daunorubicin may form complexes with metals such as iron. Although these metal-anthracycline complexes result in oxygen free radical formation, which may contribute to antitumor activity, membrane damage incurred from the free radicals is thought to be the mechanism responsible for... 

Luxemburgia nobilis Eichl. (leaves) Ochnaflavone (I-3, 0,II-4 —flavone-flavanone)-. 11-2,3-Dihydroochnaflavone (225). Inhibitor of DNA topoisomerases. (225) was cytotoxic to murine Ehrlich carcinoma and human leukemia K562 cells. (225) inhibited the activity of human DNA topoisomerases I and Il-a. (225) is a DNA interacting agent, which causes DNA unwinding in an assay with topoisomerase I. Likhitwitayawuid e al., 2001 [290] D Oliveira et al 2002[291],2005[59]. 

Yamashita Y, Kawada N, Fujii N, Nakano H. Induction of mammalian DNA topoisomerase I and II mediated DNA cleavage by saintopin, a new antitumor agent from fungus. Biochemistry 30 5838-5845, 1991. 

Rebeccamycin is a natural product that inhibits DNA topoisomerase I and has been studied as a potential anticancer agent because of the importance of DNA topoisomerase I in cell growth and proliferation. Rebeccamycin analogues are being used in clinical trials for the treatment of neoplastic tumors,renal cell cancer, and leukemia, " rehO is one of the 11 genes in the rebeccamycin biosynthetic cluster. The protein product, RebO, is an L-amino acid oxidase that contains a noncovalently bound FAD. RebO catalyzes the oxidation of 7-chloro-L-tryptophan in an early step in rebeccamycin biosynthesis (Equation (4)). 

Chowdhury AR, Mandal S, Goswami A et al. Dihydrobetulinic acid induces apoptosis in Leishmania donovani by primarily tasting DNA topoisomerase I and II Implications in antileishmanial therapy. Mol Med 2003 9 26-36. 

Malanga M, Altfaaus FR. Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and induces DNA strand break resealii. J Biol Chem 2004 279 5244-3248. 

Krzysztof B, Katarzyna W, Anna B (2006) Inhibition of DNA topoisomerases I and II, and growth inhibition of breast cancer MCF-7 cells by Ouabain, Digoxin and Proscillaridin. A Biol Pharm Bull 29 1493-1497... 

Jean-Moreno, V. Rojas, R. Goyeneche, D. Coombs, G. H. Walker, J. Leishmania donovani differential activities of classical topoisomerase inhibitors and antileishmanials against parasite and host cells at the level of DNA topoisomerase I and in cytotoxicity assays. Exp. Parasitol. 2006, 112, 21-30. 

DNA topoisomerase I and II play important roles in DNA replication and transcription. Their inhibition usually leads to cell-cycle arrest and cell death by apoptosis. During replication, DNA needs to be uncoiled. In order to avoid torsions and rotations, DNA is cleaved by DNA topoisomerase 1, which forms... 

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