ALKBH2
Domain
The PCNA-binding motif (AlkB homolog 2 PCNA-interacting motif, APIM), mediates the colocalization of ALKBH2 with PCNA at the replication foci, coordinating the repair of alkylated DNA damage with DNA replication.
Function
Dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation. Can process both double-stranded (ds) and single-stranded (ss) DNA substrates, with a strong preference for dsDNA (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:20714506, PubMed:23972994, PubMed:25797601). Uses molecular oxygen, 2-oxoglutarate and iron as cofactors to oxidize the alkyl groups that are subsequently released as aldehydes, regenerating the undamaged bases. 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 (PubMed:18432238, PubMed:22659876). 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 (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:20714506, PubMed:23972994, PubMed:25797601, PubMed:26408825). Acts as a gatekeeper of genomic integrity under alkylation stress. Efficiently repairs alkylated lesions in ribosomal DNA (rDNA). These lesions can cause ss- and dsDNA strand breaks that severely impair rDNA transcription (PubMed:23972994). In a response mechanism to DNA damage, associates with PCNA at replication forks to repair alkylated adducts prior to replication (PubMed:19736315, PubMed:26408825).
Sequence Similarities
Belongs to the alkB family.
Tissue Specificity
Detected in colon, small intestine, ovary, testis, prostate, skeletal muscle, heart, liver and urinary bladder.
Cellular localization
- Nucleus
- Nucleus
- Nucleolus
- Nucleus
- Nucleoplasm
- Relocates to the replication foci during S-phase.
Alternative names
ABH2, ALKBH2, DNA oxidative demethylase ALKBH2, Alkylated DNA repair protein alkB homolog 2, Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2, Oxy DC1