Human DNA Oxidative Demethylase ALKBH2 (ALKBH2) Protein

Background

ALKBH2 is a key DNA repair enzyme that catalyzes the direct reversal of methylated lesions, particularly N1-methyladenine (m1A) and N3-methylcytosine (m3C), in double-stranded DNA. It is part of the alpha-ketoglutarate (α-KG)- and Fe(II)-dependent dioxygenase family, where it utilizes α-KG and molecular oxygen to demethylate damaged bases. ALKBH2 is essential for maintaining genomic integrity, as it repairs alkylation damage caused by environmental mutagens, chemotherapeutic agents, and endogenous metabolism. It operates in coordination with other DNA repair pathways to prevent mutations and DNA strand breaks. ALKBH2 is particularly active during DNA replication and cell division, ensuring faithful genome transmission. Mutations or dysregulation of ALKBH2 are associated with increased susceptibility to cancer and reduced cellular survival under genotoxic stress. Its function makes it a promising therapeutic target for enhancing the efficacy of alkylating agents in cancer treatment.