ALKBH3 mediated reversal of alkylation damage

Stable Identifier
Homo sapiens
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ALKBH3, like ALKBH2, is a homolog of E.coli alpha-ketoglutarate- and Fe(II)-dependent dioxygenase AlkB that oxidizes methyl groups on alkylated DNA bases and releases them as formaldehyde. Like ALKBH2, ALKBH3 removes 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction and regenerates unsubstituted bases. Like ALKBH2, ALKBH3 can also repair 1-ethyladenine (1-etA) residues in DNA with the release of acetaldehyde (Duncan et al., 2002, Lee et al. 2005). While ALKBH2 has a preference for double strand DNA (dsDNA), ALKBH3 has a preference for single strand DNA (ssDNA). ALKBH3 efficiently repairs dsDNA in the presence of ASCC3 DNA helicase, which unwinds dsDNA, thus providing the single strand substrate for ALKBH3 (Dango et al. 2011).

Literature References
PubMed ID Title Journal Year
15040447 Repairing DNA-methylation damage.

Sedgwick, B

Nat Rev Mol Cell Biol 2004
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
16174769 Repair of methylation damage in DNA and RNA by mammalian AlkB homologues

Cai, S, Lee, DH, O'Connor, TR, Jin, SG, Pfeifer, GP, Chen, Y

J Biol Chem 2005
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