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Alkylation damage

06-AGT I plays a key role in the adaptive response and hence, it is sometimes also referred to as Ada and it is encoded by the ada gene in E. coli. It is unusual in that it becomes inactivated as a consequence of the transfer of the alkyl group to its cysteine residues and hence it is described as a suicide enzyme. 06-AGT I has dual functions one as a repair protein and the other as a transcriptional regulator of genes involved in the repair of alkylation damage. Levels of the protein increase [Pg.498]


In E. coli, repair is induced by alkylation damage. The repair of methylated DNA is performed by, among others, the Ada protein which possesses S-alkyl transferase and transcription activation activity. The Ada protein is methylated during the first repair process. In the methylated form the Ada protein can function as a transcriptional activator. It binds to the corresponding DNA element of an operon which encodes for... [Pg.33]

Landing P, Volkert MR. Regulatory responses of the adaptive 24. response to alkylation damage a simple regulon with complex regulatory features. J. Bacterial. 2000 182(23) 6543-6549. [Pg.354]

Cells are endowed with several distinct enzyme-catalyzed mechanisms that specifically effect the repair of various alkylated bases (1). The alkylating agents used experimentally to generate the multiple substrates attacked by these enzymes are, in the main, not naturally occurring. However, it is intuitively compelling that these enzymes must have evolved to cope with spontaneous forms of alkylation damage to DNA (Table 1). Support for the notion of spontaneous alkylation damage to DNA comes from several studies. [Pg.1358]

Sedgwick B. Oxidation of methylhydrazines to mutagenic methylating derivatives and inducers of the adaptive response of Escherichia coli to alkylation damage. Cancer Res. 1992 52 3693-3697. [Pg.1361]

Mehl, A., Rolseth, V., Gordon, S., Bjoraas, M., Seeberg, E., and Fonnum, F. 2000. Brain hypoplasia caused by exposure to trichlorfon and dichlorvos during development can be ascribed to DNA alkylation damage and inhibition of DNA alkyltransferase repair. Neurotoxicology, 21, 165-173. [Pg.257]

In bacteria O -alkylguanine alkyltransferase regulates both its own transcription and that of another repair enzyme, a DNA-N-glycosylase. There is evidence that the alkylated form of the alkyltransferase is the specific form of the transcriptional activator. This allows the cell to adapt to alkylation damage by using the alkylated protein as a specific signal to produce more of the proteins needed to repair the damage. [Pg.2191]

AAG (also knovm as ANPG), the only known member of its ovm structural class, is a single-domain eukaryotic monofunctional glycosylase that repairs alkylation damage (Engelward et al, 1993). Endonuclease V from the T4 virus, which also has no known structural relatives, is a small (16-kD) bifunctional glycosylase that repairs ultraviolet-induced thymine dimers (Dodson etal, 1993). [Pg.9]

Alkylated lesion bases have especially labile glycosidic bonds, and therefore require less powerful catalysis by DNA glycosylases. Accordingly, Maglll performs catalysis on alkylated substrates even when the conserved catalytic aspartate is mutated (Eichman et al, 2003). However, the alkylation damage-specific glycosylase AlkA has been shown to be a sufficiently powerful catalyst to remove normal bases from DNA (Berdal et al, 1998), and AAG exhibits a 10 -fold catalytic rate enhancement on the substrate hypoxanthine (O Brien and Ellenberger, 2003). [Pg.17]

It seems then that alkylation damage increases DNA ligase activity, and predominantly DNA ligase II activity which is presumed to be the major repair enzyme. This increase in DNA ligase II activity is totally prevented by inhibiting poly(ADP-ribose) biosynthesis, implying that the increase in DNA ligase activity requires ADPRT activity. [Pg.14]

We have examined the consequences of inhibition of chromatin-associated poly(ADP-ribosylation) on individual reaction steps of DNA repair elicited by a number of different carcinogens. In this analysis we could identify at least two ADP-ribose dependent reaction steps in the process of DNA repair, while others were found unresponsive to inhibition of nuclear ADP-ribosylation. Thus, for example, the rate of resynthesis of repair patches as well as the rate of ligation were increased in hepatocytes recovering from alkylation damage, pyrimidine dimers or bulky lesions caused by the ultimate carcinogen N-acetoxy-2-acetylaminofluorene (NAcAAF) ([9], F.R. Althaus, unpublished observations). Despite this apparent stimulation of intermediate steps of DNA repair, the removal of guanine adducts of NAcAAF (dG-8-AAF) was incomplete under conditions of inhibited ADP-ribosylation activity (F.R. Althaus and M.C. Poirier, unpublished observations). [Pg.238]

Substitution of Mn(II) for Mg(II) in DNA polymerases results in decreased fidelity (Goodman et al. 1983 Beckman et al. 1985). Under conditions where Mn(II) is not mutagenic, it enhanced UV-induced mutagenesis in E. coli (Rossman and Molina 1986). A likely explanation for the comutagenic effect is that Mn(II) affects DNA replication of a damaged template. This was shown in the case of alkylation damage, where Mn(II) facilitated postlesion synthesis which was accompanied by misincorporation opposite the alkylated bases (Bhanot and Solomon 1994). [Pg.393]

Mishina Y, Duguid EM, He C (2006) Direct reversal of DNA alkylation damage. Chem Rev... [Pg.85]


See other pages where Alkylation damage is mentioned: [Pg.53]    [Pg.639]    [Pg.32]    [Pg.975]    [Pg.438]    [Pg.498]    [Pg.499]    [Pg.499]    [Pg.500]    [Pg.500]    [Pg.501]    [Pg.301]    [Pg.53]    [Pg.354]    [Pg.735]    [Pg.1358]    [Pg.352]    [Pg.412]    [Pg.975]    [Pg.126]    [Pg.1167]    [Pg.77]    [Pg.6]    [Pg.249]    [Pg.289]    [Pg.157]    [Pg.348]    [Pg.131]    [Pg.209]    [Pg.150]   
See also in sourсe #XX -- [ Pg.498 , Pg.499 , Pg.500 , Pg.505 ]




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