NEIL1

NEIL1 stands for Nei-like DNA glycosylase 1, a member of the NEIL family of DNA repair enzymes that participate in base excision repair (BER). In humans, NEIL1 recognizes and removes a subset of oxidative DNA lesions, including certain oxidized purines and pyrimidines such as formamidopyrimidines, and to a lesser extent 8-oxoguanine compared with other BER enzymes. By excising damaged bases, NEIL1 creates abasic sites that are subsequently processed by the BER pathway to restore correct DNA sequence.

Mechanistically, NEIL1 is a bifunctional DNA glycosylase/lyase. Its glycosylase activity removes the damaged base, generating an abasic site, and its lyase activity can cleave the DNA backbone at that site, producing strand breaks with modified ends that are then processed by downstream BER enzymes such as AP endonuclease and polymerase beta. NEIL1’s action is coordinated with other BER factors, and its activity is thought to be particularly important during DNA replication, where lesions encountered by the replication machinery need prompt repair to prevent mutagenesis or fork collapse. The enzyme has a conserved active site lysine that participates in forming a covalent intermediate with the abasic sugar during the repair process.

Localization of NEIL1 includes both the nucleus and mitochondria, enabling repair of oxidative DNA damage in nuclear and mitochondrial genomes. It is widely expressed across tissues and can be upregulated in response to oxidative stress. NEIL1 belongs to the Nei-like DNA glycosylase family, along with NEIL2 and NEIL3, sharing a common catalytic mechanism and structural features.

Genetic and functional studies indicate that NEIL1 contributes to genome stability, with loss- or variation-associated defects in repair capacity linked to increased sensitivity to oxidative damage and potential links to cancer susceptibility in model systems and human populations.