title: A DNA oligomer containing 2,2,4-triamino-5(2H)-oxazolone is incised by human NEIL1 and NTH1.
abstract: The nucleobase derivative, 2,2,4-triamino-5(2H)-oxazolone (Oz), is an oxidation product of guanine or of 8-oxo-7,8-dihydroguanine that causes G-to-C transversions in DNA. Human NEIL1 (hNEIL1) and NTH1 (hNTH1) are homologues of two prokaryotic base excision repair enzymes, FPG/NEI and NTH, respectively. Here, we demonstrated that hNEIL1 and hNTH1 cleave Oz sites as efficiently as 5-hydroxyuracil sites. Thus, hNEIL1 and hNTH1 can repair Oz lesions. Furthermore, the nicking activities of these enzymes are largely independent of nucleobases opposite Oz; this finding indicates that removing Oz from Oz:G and Oz:A base pairs might cause an increase in the rate of point mutations in human cells.
authors.affiliation: Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan. kkino@kph.bunri-u.ac.jp
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Kino
authors.forename: Masashi
authors.initials: M
authors.lastname: Takao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazawa
authors.forename: Fumio
authors.initials: F
authors.lastname: Hanaoka
mesh_terms: D045647:DNA Glycosylases / Q000235:genetics*; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000235:genetics*; D006147:Guanine / Q000378:metabolism; D006801:Humans; D010081:Oxazolone / Q000378:metabolism*; D010084:Oxidation-Reduction; D017354:Point Mutation
chemical_list: D010081:Oxazolone; D006147:Guanine; D043224:Deoxyribonuclease (Pyrimidine Dimer); C468347:NTHL1 protein, human; D045647:DNA Glycosylases; C473634:NEIL1 protein, human