PMID:12517444
| Citation |
Begley, TJ and Samson, LD (2003) AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism. Trends Biochem. Sci. 28:2-5 |
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| Abstract |
All organisms have multiple DNA repair pathways to protect against alkylation-induced mutation and cell death. For nearly two decades, we have known that the Escherichia coli alkB gene product protects against cell killing by S(N)2-alkylating agents, probably through DNA repair. Despite numerous attempts, a specific DNA repair activity could not be assigned to AlkB. Now, a breakthrough in biology and biochemistry, coupled with the discovery of an in silico protein structure, has uncovered a novel direct reversal DNA repair mechanism that is catalyzed by AlkB, namely the oxidative demethylation of N1-methyladenine or N3-methylcytosine DNA lesions. This reaction occurs on both single- and double-stranded DNA, and requires AlkB-bound non-heme Fe(2+), O(2) and alpha-ketogluterate to oxidize the offending methyl group. This is followed by the release of succinate, CO(2) and formaldehyde, and the restoration of undamaged A or C in DNA. |
| Links | |
| Keywords |
Adenine/analogs & derivatives; Adenine/metabolism; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Catalysis; Cytosine/analogs & derivatives; Cytosine/metabolism; DNA Damage/genetics; DNA Methylation; DNA Repair; DNA, Single-Stranded/metabolism; Escherichia coli Proteins; Mixed Function Oxygenases; Oxidation-Reduction; Protein Binding |
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