N-terminal domain of metazoan Nei-like glycosylase 2 (NEIL2)
This family contains the N-terminal domain of the metazoan protein Neil2. It belongs to the FpgNei_N, [N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII)] domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. NEIL2 repairs 5-hydroxyuracil (5-OHU) and other oxidized derivatives of cytosine, but it shows preference for DNA bubble structures. In addition to this MeNeil2_N domain, NEIL2 contains a helix-two turn-helix (H2TH) domain and a characteristic CHCC zinc finger motif. Neil2 is one of three homologs found in eukaryotes.