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    Trends Biochem Sci. 2003 Jan;28(1):2-5.

    AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism.

    Begley TJ, Samson LD.

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    Biological Engineering Division and Center for Environmental Health Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.

    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.

    PMID:
    12517444
    [PubMed - indexed for MEDLINE]

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