Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage (PubMed:9927729). The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N-glycosidic bond, leaving an AP site. The AP-lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines. Has also 8-oxo-7,8-dihydroguanine (8-oxoG) DNA glycosylase activity. Acts preferentially on DNA damage opposite guanine residues in DNA. Is able to process lesions in nucleosomes without requiring or inducing nucleosome disruption. 2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)-2'-deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3-dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-monophospho-2'-deoxyribonucleoside-DNA + H(+) Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a role in catalysis, but is probably involved in the proper positioning of the enzyme along the DNA strand. APE1 displaces NTHL1 from the N-glycosylase-generated AP site in DNA, thereby increasing the turnover of the DNA N-glycosylase activity (PubMed:11287425, PubMed:12519758). AP lyase activity is stimulated by YBX1 (PubMed:11287425). ERCC5/XPG stimulates NTHL1 activity and NTHL1 binding to its DNA substrate (PubMed:9927729). Interacts with YBX1 (By similarity) (PubMed:11287425). Interacts with ERCC5/XPG; the interaction stimulates NTHL1 activity and NTHL1 binding to its DNA substrate (PubMed:9927729). Widely expressed with highest levels in heart and lowest levels in lung and liver. Expression levels are regulated during the cell cycle with increased levels during early and mid S-phase. The disease is caused by variants affecting the gene represented in this entry. Belongs to the Nth/MutY family.