Ada DNA repair protein

Figure 12.8 Some other active-site coordination motifs in mononuclear zinc enzymes from left to right bacteriophage T7 lysozyme, 5-aminolaevulinate dehydratase, Ada DNA repair protein. (Reprinted with permission from Parkin, 2004. Copyright (2004) American Chemical Society.)...

FIGURE 12.13 Repair of damaged DNA by sacrificial alkylation of one of the zinc cysteine thiolate ligands of the Ada DNA repair protein. 

There has been much recent interest in the role of zinc in activating cysteine residues to nucleophilic attack.542-545 Alkyl group transfer to coordinated cysteine residues occurs in a number of zinc proteins, such as Ada (the E. coli DNA repair protein) and the cobala-... 

Fig. 1.25. Regulation of alkylation repair in E. coK by methylation of the Ada protein. The effect of methylating agents, such as N-nitroso-N-methyl urea lead to the formation of methyl phospho-triesters (P-Me) of DNA, as well as various base adducts. The Ada protein possesses an N-termi-nal and a C-terminal domain. In one of the first steps of alkylation repair the methyl groups of the phosphotriester is transferred to the Ada protein. The Ada protein is methylated on a Cys residue at its N-terminal domain and thereby transformed into an active transcription activator. In its methylated form the Ada protein binds to the control region of various genes to stimulate their transcription. Among the genes under the control of the Ada protein are its own gene, as well others required for DNA repair (alkB, alkA). After Lindahl et al., 1988.

Ada and other proteins. Upon the binding of the methylated Ada protein to its cognate DNA element, the transcription of the genes is stimulated such that more repair proteins are available. 

There are other types of transcriptional activators in bacteria. One is transcription factor 1 (TF1) encoded by a Bacillus subtilis phage. It is a member of the protein HU family (Chapter 27). However, unlike the nonspecific HU it binds to some sites specifically and activates transcription.143 The E. coli Ada protein is the acceptor protein in removal of methyl groups from DNA (Chapter 27). The same protein is an inducer of transcription of DNA repair enzymes in the large ada regulon. Methylation of Cys 69 of the Ada protein itself converts it into a gene activator.144... 

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... 

---