Nei-like DNA glycosylase 3 (NEIL3)

NEIL3 is a bifunctional DNA glycosylase and AP lyase enzyme that initiates the base excision repair pathway, specializing in the recognition and excision of oxidatively damaged DNA bases, particularly in single-stranded DNA regions, G-quadruplex structures, and sites of DNA interstrand crosslinks[1][4]. NEIL3 expression is highest in cells with strong proliferative capacity (such as embryonic, thymus, spleen, bone marrow, and cancer cells), where it is tightly cell cycle regulated[1][5]. Structurally, NEIL3 contains an Fpg/Nei-like catalytic core and unique C-terminal glycine-arginine-phenylalanine zinc finger motifs that enable specific DNA and protein interactions[1][2]. NEIL3 is essential for maintaining genome stability during DNA replication by repairing lesions at replication forks and telomeres, and by excising DNA adducts formed by agents like psoralen and cisplatin[2][4]. Dysfunction or overexpression of NEIL3 has been linked to cancer development, prognosis, and therapy resistance, as well as roles in cardiovascular and neurological diseases[1]. NEIL3 is emerging as a prognostic marker and potential therapeutic target, especially where modulation of DNA repair may be beneficial[1][2].

Other names

Endonuclease 8-like 3DNA glycosylase FPG2DNA glycosylase/AP lyase Neil3hFPG2FPG2hNEI3ZGRF3Nei-like protein 3zinc finger GRF-type containing 3

Drugs like cisplatin induce DNA crosslinks and oxidative damage; NEIL3 participates in the repair of lesions from these agents via the base excision repair pathway, conferring resistance to such drugs[2].