Endonuclease 4 (Endo IV) (Endo IV)

Endonuclease IV (Endo IV), encoded by the nfo gene in Escherichia coli, is a vital DNA repair enzyme belonging to the Class II AP endonuclease family (UniProt P0A6B7). It plays a critical role in the base excision repair (BER) pathway by recognizing and cleaving the phosphodiester backbone at apurinic/apyrimidinic (AP) sites, which are common DNA lesions resulting from spontaneous hydrolysis or oxidative damage (PubMed: 2631424). Unlike the more abundant Exonuclease III, Endonuclease IV is specifically induced by oxidative stress and is capable of removing a variety of 3'-blocking groups, such as 3'-phosphoglycolate and 3'-phosphate, to facilitate DNA polymerase activity (PubMed: 2983314). Structurally, it is a TIM-barrel protein that utilizes a tri-zinc center to catalyze the hydrolysis of the DNA backbone (PDB: 1QTW). While not a primary human therapeutic target, it is investigated as an antimicrobial target to sensitize bacteria to DNA-damaging agents and oxidative stress (PubMed: 16439568). Inhibition of this enzyme can lead to the accumulation of lethal DNA breaks in bacterial cells, particularly when combined with other stressors. It serves as a model for understanding the repair of oxidative DNA damage across various species.

Other names

nfoEndonuclease IVApurinic-apyrimidinic endonuclease IVAP endonuclease 2

Endonuclease IV catalyzes the hydrolysis of the phosphodiester bond 5' to an abasic site, generating a 3'-hydroxyl group and a 5'-deoxyribose-5-phosphate (dRP) terminus (PubMed: 2631424).