Oxidative demethylation of 1-meA damaged DNA By ALKBH3

Stable Identifier
Reaction [transition]
Homo sapiens
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ALKBH3, a homolog of E.coli AlkB (Trewick et al. 2002), removes the methyl group from 1-methyladenine (1-meA) in a reaction dependent on alpha-ketoglutarate, oxygen and Fe2+. ALKBH3 directly reverses alkylating damage of DNA in the form of 1-meA that is accompanied with the release of formaldehyde (Duncan et al. 2002). The reversal of alkylating damage of dsDNA by ALKBH3 requires the presence of DNA helicase ASCC3, a component of the activating signal co-integrator complex (Dango et al. 2011). ALKBH3 can also repair methylated RNA (Aas et al. 2003).

Literature References
PubMed ID Title Journal Year
12226667 Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage.

Lindahl, T, Henshaw, TF, Hausinger, RP, Sedgwick, B, Trewick, SC

Nature 2002
12594517 Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA

Falnes, PO, Otterlei, M, Seeberg, E, Akbari, M, Slupphaug, G, Vågbø, CB, Bjørås, M, Skorpen, F, Aas, PA, Sundheim, O, Krokan, HE

Nature 2003
22055184 DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation

Xiong, LJ, Park, K, Mosammaparast, N, Dango, S, Shi, Y, Gygi, S, Sowa, ME, Harper, JW, Wu, F, Rubin, M

Mol. Cell 2011
12486230 Reversal of DNA alkylation damage by two human dioxygenases.

Lindahl, T, Duncan, T, Bates, PA, Sedgwick, B, Trewick, SC, Koivisto, P

Proc Natl Acad Sci U S A 2002
Catalyst Activity

DNA-N1-methyladenine dioxygenase activity of ALKBH3:Fe2+:ASCC1:ASCC2:ASCC3:1-meA-dsDNA [nucleoplasm]

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