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DNA Repair (Amst). 2013 Dec;12(12):1159-64. doi: 10.1016/j.dnarep.2013.04.026. Epub 2013 Jun 5.

Human NEIL3 is mainly a monofunctional DNA glycosylase removing spiroimindiohydantoin and guanidinohydantoin.

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Department of Microbiology, University of Oslo, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, NO-0424 Oslo, Norway.


Base excision repair is the major pathway for removal of oxidative DNA base damage. This pathway is initiated by DNA glycosylases, which recognize and excise damaged bases from DNA. In this work, we have purified the glycosylase domain (GD) of human DNA glycosylase NEIL3. The substrate specificity has been characterized and we have elucidated the catalytic mechanisms. GD NEIL3 excised the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in single-stranded (ss) and double-stranded (ds) DNA efficiently. NEIL3 also removed 5-hydroxy-2'-deoxycytidine (5OHC) and 5-hydroxy-2'-deoxyuridine (5OHU) in ssDNA, but less efficiently than hydantoins. Unlike NEIL1 and NEIL2, which possess a β,δ-elimination activity, NEIL3 mainly incised damaged DNA by β-elimination. Further, the base excision and strand incision activities of NEIL3 exhibited a non-concerted action, indicating that NEIL3 mainly operate as a monofunctional DNA glycosylase. The site-specific NEIL3 mutant V2P, however, showed a concerted action, suggesting that the N-terminal amino group in Val2 is critical for the monofunctional modus. Finally, we demonstrated that residue Lys81 is essential for catalysis.


2,6-diamino-4-hydroxy-5-formamidopyrimidine; 5-hydroxy-2′-deoxycytidine; 5-hydroxy-2′-deoxyuridine; 5OHC; 5OHU; AP; BER; Base excision repair; CV; DNA damage; DNA glycosylase; E. coli endonuclease VIII; E. coli endonuclease VIII-like; Escherichia coli formamidopyrimidine DNA glycosylase; Fpg; GD; Gh; H2TH; Human NEIL3; MCS; Mouse Neil3; NEIL; Nei; Nth; Oxidation; ROS; Sp; UDG; apurinic/apyrimidinic; base excision repair; column volume; core glycosylase domain; double-stranded; ds; endonuclease III; faPy; guanidinohydantoin; helix-two-turn-helix; multiple cloning site; reactive oxygen species; single-stranded; spiroiminodihydantoin; ss; uracil DNA glycosylase

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