Inhibition of DNA replication

Cross-linkage - bifunctional agents may form covalent bonds with each of two adjacent guanine residues and such inter-strand cross-links will lead to inhibition of DNA replication and transcription. Intra-strand and DNA-protein cross-links may also be formed ... 

The alkylating drugs are the oldest category of chemotherapy agents. Globally, cytoxocity results from inhibition of DNA replication because interlinked strands do not separate. 

Xu X, Hamhouyia F, Thomas SD, Burke TJ, Girvan AC, McGregor WG, Trent JO, Miller DM, Bates PJ (2001) Inhibition of DNA replication and induction of S phase cell cycle arrest by G-rich oligonucleotides. J Biol Chem 276 43221-43230... 

MV Davies, J Pelletier, K Meerovitch, N Sonenberg, RJ Kaufman. The effect of poliovirus proteinase 2Apro expression on cellular metabolism. Inhibition of DNA replication, RNA polymerase II transcription, and translation. J Biol Chem 266 14714-14720, 1991. 

Cisplatin-DNA lesions have been shown to interfere with DNA replication and transcription [2-4], Inhibition of DNA replication can produce... 

The difference in cell sensitivity to cisplatin as a function of the cell cycle can be a useful tool to examine the role played by the inhibition of DNA replication in the drug-induced toxicity. This point was addressed by a study [62] which showed that cells treated with 6 pg/ml in the G1 phase, before the start of DNA replication, exhibited a ten-hour cell-division delay during the first cell cycle after treatment, whereas the delay was only of three hours if the treatment occurred in the late S-phase when most of the DNA replication was terminated. In addition, more chromosomal aberrations were detected following treatment in the G1 phase. The different responses of the cells treated with cisplatin in G1 v.v. cells treated in the late... 

Sunlight is able to inactivate microorganisms due to the synergistic effect of the UV and IR parts of sunlight. The main type of UV-B-induced DNA lesions consists in the formation of dimeric pyrimidine photoproducts cause inhibition of DNA replication and also bacterial mutations (Britt 1996). 

The anticancer activity of daunomycin (34) (O Scheme 14) is attributed to the intercalation of the drug with DNA. This pattern of effect is common to all anthracyclines [46]. Two daunomycin molecules intercalate at each of the two C G sites at either site of the duplex d(CGTACG). This binding results in an increase in base pair-separation from 3.4 to 6.8 A as the molecule associates, which in turn leads to an unwinding of the helix and the formation of a noncovalent complex with the DNA. This results in the inhibition of DNA replication and RNA transcription [47]. 

DNA-DNA and DNA-protein cross-links inhibition of DNA replication selective cytotoxicity for myeloid cells crosses blood-brain barrier... 

Replication of DNA requires the separation of the two companion strands of the parental double-helical structure, and substances that interfere with strand separation should inhibit DNA replication. Moreover, RNA transcription from DNA requires the availability of certain base pairs, and constraint of these pairs will hinder the process. Thus, one of the modes of action of chloroquine, quinacrine, and quinine, and their congeners, is an inhibition of DNA replication primarily, but also of. RNA transcription from DNA secondarily, mediated throu inhibition of the respective DNA and RNA polymerase reactions. Whether these processes take place in vivo... 

Many quinazolinone-based compounds function as thymidylate synthase inhibitors by directly binding to the active site of thymidylate synthase. This results in the inhibition of DNA replication as well as DNA damage, S-phase cell arrest, and caspase-dependent apoptosis. Many compounds of this class have been successfully employed as anti-cancer pharmaceutics. Two examples, nolatrexed, a compound used to treat unresectable hepatocellular carcinoma (HCC), and raltitrexed, a first-line treatment against advanced colorectal cancer, are highlighted below. 

C19H24N2O9 424.407 A component of Novobiocin. Shows the same potency as Novobiocin and is prob. the active moiety in inhibition of DNA replication. 

Hamburg-Eppendorf, Hamburg, Germany), b Inhibition of DNA replication after exposure to IR. Replication activity was measured via incorporation of radioactively labeled thymidine (data are from Painter 1986). c Delay in G2, as detected in the mutant p53 human squamous cell carcinoma strain FaDu after irradiation with 6 Gy. Exponentially growing cells were irradiated with 6 Gy, and the cell cycle distribution was measured by flow cytometry... 

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