Endonuclease VIII-like 1 (NEIL1)

Endonuclease VIII-like 1 (NEIL1) is a DNA glycosylase and AP lyase critical in the base excision repair (BER) pathway, where it recognizes and removes oxidized DNA lesions produced by reactive oxygen species. NEIL1 excises a spectrum of oxidized bases, particularly ring-opened purines like FapyA and FapyG, and is active on both double-stranded and single-stranded DNA, as well as on DNA substrates relevant to replication and transcription. It interacts with multiple DNA repair and replication proteins, including PCNA, FEN-1, WRN, XRCC1, and PARP-1, integrating it into broader cellular responses to DNA damage. NEIL1's activity is cell-cycle regulated and particularly important in S phase, preventing replication-associated mutagenesis by pre-replicative repair of damaged bases. NEIL1 is widely expressed, especially in tissues with high metabolic activity, and is essential for maintaining genomic stability and protecting against cell death—especially in neurons during ischemic brain injury and potentially in aging, cancer, and metabolic disease. NEIL1 deficiencies lead to increased DNA damage, apoptosis, neurological impairment, and susceptibility to tissue injury under oxidative stress conditions. No currently approved drugs directly modulate NEIL1 activity, but broader DNA repair modulation may affect its function.

Other names

Endonuclease 8-like 1FPG1NEH1hFPG1DNA glycosylase/AP lyase Neil1DNA-(apurinic or apyrimidinic site) lyase Neil1Nei homolog 1Nei-like protein 1DNA endonuclease eight-like glycosylase 1

Drugs targeting the broader DNA repair machinery (e.g., PARP inhibitors) may indirectly impact NEIL1 function by altering the DNA repair environment. Hypothetically, a direct NEIL1 inhibitor would block base excision repair of oxidized DNA bases, leading to accumulated DNA damage and increased sensitivity to oxidative stress.