Human AlkB Homolog 3, Alpha-Ketoglutaratedependent Dioxygenase (ALKBH3) Protein

Background

ALKBH3 is an α-KG- and Fe(II)-dependent dioxygenase that repairs methylated lesions on single-stranded DNA (ssDNA) and RNA. It specifically removes alkylation damage, such as N1-methyladenine (m1A) and N3-methylcytosine (m3C), restoring nucleic acid integrity and ensuring proper transcription and translation. ALKBH3 exhibits a preference for repairing damage in RNA, including tRNA, rRNA, and mRNA, where it preserves their structural stability and functionality. ALKBH3 interacts with ASCC3 helicase, which unwinds damaged regions of DNA/RNA, facilitating repair. Its role in RNA demethylation highlights its importance in regulating gene expression and protein synthesis. Overexpression of ALKBH3 has been observed in various cancers, including prostate, pancreatic, and lung cancers, where it contributes to tumor cell proliferation, survival, and resistance to alkylating agents. Targeting ALKBH3 has been explored as a therapeutic approach for sensitizing cancer cells to chemotherapy and inhibiting tumor growth.