Nth like DNA glycosylase 1 (NTHL1)

Nth like DNA glycosylase 1 (NTHL1) is a bifunctional DNA glycosylase/AP lyase enzyme critical for the base excision repair (BER) pathway, specifically recognizing and excising oxidatively damaged pyrimidine bases from DNA, with subsequent cleavage at the abasic site[1][2][6][7][8]. NTHL1 is evolutionarily related to Escherichia coli endonuclease III but has adapted unique substrate specificity and regulation in mammals, including a non-conserved disordered N-terminal domain that modulates enzymatic turnover[4]. Its normal function is essential for genomic integrity and prevention of spontaneous mutagenesis. Defects—either loss-of-function mutations or pathogenic overexpression—can induce genomic instability and are associated with various cancers, particularly colorectal polyposis syndromes[1][2][4][7]. Mechanistically, NTHL1 removes oxidized pyrimidines such as thymine glycol and 5-hydroxycytosine, triggering BER and coordinating with repair partners including XPG; dysregulation may interfere with other repair pathways and homologous recombination, further increasing mutational burden[2][5]. NTHL1 is therefore considered both a "caretaker" tumor suppressor and a potential marker for inherited predisposition to cancer[8].

Other names

Endonuclease III-like protein 1NTHL1NTH1hNTH1OCTS3DNA glycosylase/AP lyaseFAP3Bifunctional DNA N-glycosylase/DNA-(apurinic or apyrimidinic site) lyasenth endonuclease III-like 1

For drugs: No direct drugs targeting NTHL1 described; mechanism relevant for DNA damaging agents includes increased sensitivity via impaired repair pathways in context of NTHL1 dysregulation