Modulation of mutagenesis

Modulation of Mutagenesis by 3-carotene and 13-cis-Retinoic Acid. The provitamin 3-carotene, and a synthetic derivative of vitamin A, 13-cis-retinoic acid, were examined with respect to their capacity to modulate 2-fluorenamine-induced mutagenicity in Salmonella. These studies were carried out since dietary and serum levels of 3-carotene vary widely among humans. Also, there is considerable interest in the anti-tumor activity of 13-cis-retinoic acid and other synthetic retinoids. 

Pariza, M.W., Loretz, L.J., Storkson, J.M., and Holland, N.C. (1983) Mutagens and Modulator of Mutagenesis in Fried Ground Beef, Cancer Res. 43 (Suppl), 2444S-2446S. 

Kortenkamp A, Oetken G, Beyersmann D (1990) The DNA cleavage induced by chromium(V) complex and by chromium and glutathione is mediated by activated oxygen species. Mutation Res 232 155-161 Kunz BA, Kohalmi SE (1991) Modulation of mutagenesis by deoxyribonucleoside levels. Annu Rev Genet 25 339-359... 

Very important reactions related to the antioxidant properties of vitamin C are reactions with active oxygen forms, with free radicals and with oxidised forms of vitamin E, respectively, which protects vitamin E and Kpid membranes from oxidation. Vitamin C has a protective function for labile forms of folic acid. It also inhibits formation of nitrosamines and acts in this way as a modulator of mutagenesis and carcinogenesis. Many other activities of vitamin C are still only partially understood or not even at all. 

De Flora, S., Bagnasco, M., and Vainio, H., Modulation of genotoxic and related effects by carotenoids and vitamin A in experimental models mechanistic issues, Mutagenesis, 14, 153-172, 1999. 

Ramos A, Olano C, Brana AF et al (2009) Modulation of deoxysugar transfer by the elloramycin glycosyltransferase ElmGT through site-directed mutagenesis. J Bacteriol 191 2871-2875... 

II) has also proven to be viable and is more convenient when using cassette mutagenesis to perform many manipulations at once. For example, a short linker modeled after the last module of the rapamycin PKS has been used to delete many of the (I-keto processing domains of DEBS [55]. Introduction of p-keto-processing activities, or gain-of-function mutagenesis, represents a more difficult... 

Baird, M.B. (1985) Modulation of Chemical Mutagenesis in a Salmonella/Mamalian Tissue Bioassay by Vitamin A and Other Retinoids. This Volume. 

Ferreira, F., C. Ebner, B. Kramer, G. Casari, P. Briza, A. J. Kungl, R. Grimm, B. Jahn-Schmid, H. Breiteneder, D. Kraft, M. Breitenbach, H. J. Rheinberger, and O. Scheiner. 1998. Modulation of IgE reactivity of allergens by site-directed mutagenesis Potential use of hypoallergenic variants for immunotherapy. FASEB J 12 (2) 231-242. 

As in rhodopsin, the residue at position 3.49 in adrenergic and other class A GPCRs, an aspartate, has been proposed as an important modulator of the transition from the inactive (R) to the active (R ) state, and not surprisingly, chargeneutralizing mutations of D3.49 in several such receptors have been shown to resultin constitutive activity (66,156-159). With the a1B-AR, mutagenesis stud-... 

Figure 19 Epothilone biosynthesis and novel derivatives generated by genetic engineering. Domains with an asterisk are assumed to be inactive. The hydroxyl group formed by the KR domain in module 4 is dehydrated by the DH domain found in module 5. Module 4 incorporates either malonyl-CoA or methylmalonyl-CoA extender units (the figure only shows the incorporation of malonyl-CoA). Epothilone derivatives generated by genetic engineering are shown in boxes (see text) and the sites of mutagenesis are indicated.

Broschard, T.H., Koffel-Schwartz, N., and Fuchs, R.P.P. (1999) Sequence-dependent modulation of frameshift mutagenesis at the Narl-derived mutation hot spots. 

Thioredoxin behaves differently from other proteins. Because of the great interest of the sulphur function in this enzyme (it is the active site of this thiol-disulfide oxidoreductase), the reduction of oxidized thioredoxin was studied in detail (139, 140). The disulfide radical is much more acidic than in other proteins, and its decay leads only to the reduced protein. Site-directed mutagenesis was used to modify selectively two amino-acids, Asp30 and Trp35, in order to observe the modulation of the redox properties of the sulphur functions. It was thus shown that both residues play a role in the proton transfer associated to electron transfer, although differently for instance, removal of W35 increases the pKa of... 

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