DNA repair process

Researchers found that NAD serves as a substrate in poly(ADP-ribose) synthesis, a reaction important for DNA repair processes. In addition, it takes part in mono (ADP-ribosyl)ation reactions that are involved in endogenous regulation of many aspects of signal transduction and membrane trafficking in eukaryotic cells. 

Flavin-cyclobutane pyrimidine dimer and flavin-oxetane model compounds like 1-3 showed for the first time that a reduced and deprotonated flavin is a strong photo-reductant even outside a protein environment, able to transfer an extra electron to cyclobutane pyrimidine dimers and oxetanes. There then spontaneously perform either a [2n+2n cycloreversion or a retro-Paternd-Buchi reaction. In this sense, the model compounds mimic the electron transfer driven DNA repair process of CPD- and (6-4)-photolyases. 

Fission yeast S. pombe is also referred to as safe - it was used for beer production in South Africa. Along with S. cerevisiae it is a very well established tool for studying basic biological processes like control of cell cycle and DNA repair processes [88], and its genome sequence is known [89]. 

Numerous studies were dedicated to the effects of flavonoids on microsomal and mitochondrial lipid peroxidation. Kaempferol, quercetin, 7,8-dihydroxyflavone and D-catechin inhibited lipid peroxidation of light mitochondrial fraction from the rat liver initiated by the xanthine oxidase system [126]. Catechin, rutin, and naringin inhibited microsomal lipid peroxidation, xanthine oxidase activity, and DNA cleavage [127]. Myricetin inhibited ferric nitrilotriacetate-induced DNA oxidation and lipid peroxidation in primary rat hepatocyte cultures and activated DNA repair process [128]. 

Downstream from DNA damage, p53 is accumulated into cell nucleus and activates the transcription of Bax (Findley et al, 1997). Therefore, Bax levels will depend on the length of the DNA repair process. If the amoimt of Bax overcomes a given threshold, ceU will activate apoptosis, thereby removing a cell potentially transformed by incomplete DNA repair. 

The production of chromosomal abnormalities by ozone was first observed in plants by Fetner, who noted abnormal anaphases in the root tips of Vicia fava seeds exposed to ozone. Bacterial mutagenesis by ozone has been reported by a number of investigators. Hamelin and Chung noted an increased mutation rate in Escherichia coli exposed to ozone at as low as 0.05 ppm for 5 min and observed that the mutants were sensitive to ozone and X irradiation. They suggested that ozone might interact in DNA repair processes. Other studies indicating ozone-induced... 

The specific interaction of chemicals or radiation with DNA activate cdlular DNA repair processes which appear to play an important role in carcinogenesis. Eukaryotic cells show enhanced repair capacity for repair of viral nucleic add if the host cells are first damaged by chemicals or irradiation. The ihanced susceptibility to cancer of patients with defective repair systems, such as those with xeroderma pigmentosum, suggests that intact repair mechanisms are protective... 

If these occur in critical genes, such as the tumor suppressor gene p53 [45], they can lead to mutations and ultimately cancer, if the mistakes are not identified and corrected by DNA repair processes. 

When base selection and proofreading are combined, DNA polymerase leaves behind one net error for every 106 to 108 bases added. Yet the measured accuracy of replication in E. coli is higher still. The additional accuracy is provided by a separate enzyme system that repairs the mismatched base pairs remaining after replication. We describe this mismatch repair, along with other DNA repair processes, in Section 25.2. 

The number and diversity of repair systems reflect both the importance of DNA repair to cell survival and the diverse sources of DNA damage (Table 25-5). Some common types of lesions, such as pyrimidine dimers (see Fig. 8-34), can be repaired by several distinct systems. Many DNA repair processes also appear to be extraordinarily inefficient energetically—an exception to... 

The clinical usefulness of cis-Pt is often limited by the development of resistance. The development of resistance to cis-Pt has been explained by several factors, including reduced drug accumulation, increased DNA repair processes, and an increase in the amount of inactivation proteins. In most cis-Pt-resistant tumors probably a combination of such factors plays a role. In this section, only an increase in cellular thiols in relation to resistance will be discussed. Such inactivation processes have already been discussed (Section IV,B), but attention will be directed now to the mechanism of resistance. These mechanisms are probably also of importance for the inactivation of cis-Pt in nonre-sistant tumors, though to a lesser extent. 

A final check of the fidelity of replication is made after a new strand has been formed. Mismatched base pairs are identified, and the incorrect nucleotides are cut out and replaced by correct ones.655 670 681 683 Some of the thymine dimers created by the action of light are also repaired photochemically by photolyases (see Chapter 23). Photoreactivation was the first DNA repair process recognized.684 However, most thymine... 

O Neill P (1983) Pulse radiolytic study of the interaction of thiols and ascorbate with OH-adducts of dGMP and dG. Implications for DNA repair processes. Radiat Res 96 198-210 O Neill P (1984) Hydroxyl radical damage potential repair by sulphydryls, ascorbate and other antioxidants. Life Chem Rep Suppl Ser 2. In Rotilio G, Bannister JV (eds) Oxidative damage and related enzymes. Life Chem Rep 1 337-341... 

Dizdaroglu M (1985) Application of capillary gas chromatography-mass spectrometry to chemical characterization of radiation-induced base damage of DNA implications for assessing DNA repair processes. Anal Biochem 144 593-603... 

Some inhibitory activity of gossypol against mouse mammary adenocarcinoma 755 and borderline activity against leukaemia P388 were reported [323, 324], The effective dose range of gossypol is rather narrow because of toxicity [324]. Gossypol has recently been found to be a specific inhibitor of DNA polymerase a [325], a major enzyme involved in DNA replication. This compound may also interfere with the DNA repair process [325]. 

SCE production is probably caused by S-phase-dependent chemicals. Consequently, DNA repair phenomena that remove lesions from DNA before lymphocytes cure stimulated to enter the S phase can influence the yield of SCEs just as they can influence the yield of chromosomal aberrations. Thus, DNA repair processes and other factors that influence SCE production still make the mechanistic interpretation of SCE production complicated when one is monitoring human populations for small exposure to chemicals.230... 

The natural DNA repair process (enzymatic) is mimicked by unsensitized irradiation of pyr-imidinedione dimers as, for example, compound (40 R = 2,5-dimethoxybenzyl) yielding the uracil derivatives (41 R = H and 2,5-dimethoxybenzyl) <93JA850>. 

The in vivo mammalian micronucleus test is used to assess the mutagenic hazard in consideration of factors like in vivo metabolism, pharmacokinetics and DNA-repair processes, although these may vary among species and among tissues. This assay is an important part of the gentox testing battery, applied for pharmaceuticals and chemicals. 

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