ALKBH2
Description
The ALKBH2 (alkB homolog 2, alpha-ketoglutarate dependent dioxygenase) is a protein-coding gene located on chromosome 12.
ALKBH2 is a dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation. It can process both double-stranded (ds) and single-stranded (ss) DNA substrates, with a strong preference for dsDNA. ALKBH2 uses molecular oxygen, 2-oxoglutarate and iron as cofactors to oxidize the alkyl groups that are subsequently released as aldehydes, regenerating the undamaged bases. It probes the base pair stability, locates a weakened base pair and flips the damaged base to accommodate the lesion in its active site for efficient catalysis. ALKBH2 repairs monoalkylated bases, specifically N1-methyladenine and N3-methylcytosine, as well as higher order alkyl adducts such as bases modified with exocyclic bridged adducts known as etheno adducts including 1,N6-ethenoadenine, 3,N4-ethenocytosine and 1,N2-ethenoguanine. ALKBH2 acts as a gatekeeper of genomic integrity under alkylation stress. It efficiently repairs alkylated lesions in ribosomal DNA (rDNA). These lesions can cause ss- and dsDNA strand breaks that severely impair rDNA transcription. In a response mechanism to DNA damage, ALKBH2 associates with PCNA at replication forks to repair alkylated adducts prior to replication.
ALKBH2 is also known as ABH2.
