ALKBH2

ALKBH2, short for AlkB homolog 2, is a human enzyme encoded by the ALKBH2 gene. It belongs to the AlkB family of non-heme iron(II)/α-ketoglutarate-dependent dioxygenases and functions as a DNA repair catalyst that reverses alkylation damage in nucleic acids. ALKBH2 preferentially demethylates certain methylated bases in double-stranded DNA, notably N1-methyladenine and N3-methylcytosine, a substrate specificity that distinguishes it from some related AlkB family members that act more effectively on single-stranded substrates.

The enzyme operates through a conserved catalytic mechanism in which Fe2+ and α-ketoglutarate (2-oxoglutarate) are required cofactors. Oxygen is activated at the metal center to hydroxylate the methyl group on the damaged base, converting it to formaldehyde and restoring the unmodified base. In the process, 2-oxoglutarate is decarboxylated to succinate and CO2. The overall result is the repair of alkylation lesions that can impede replication and transcription.

ALKBH2 is primarily localized to the nucleus and associates with chromatin during DNA repair. It is widely expressed across human tissues and is conserved in other organisms as part of the AlkB family. Functionally, ALKBH2 contributes to cellular tolerance of alkylating DNA damage and influences cellular responses to alkylating agents; loss or inhibition of ALKBH2 can increase sensitivity to such damage, while normal activity supports genome stability.