ALKBH3 mediated reversal of alkylation damage

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. 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.

Summary from Reactome (R-HSA-112126), read 2026-09-23.