A DNA oligomer containing 2,2,4-triamino-5(2H)-oxazolone is incised by human NEIL1 and NTH1

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• 作者：Katsuhito Kino^a ; ^{kkino@kph.bunri-u.ac.jp} ; Masashi Takao^b ; Hiroshi Miyazawa^a ; Fumio Hanaoka^c ; ^d ; ^{fumio.hanaoka@gakushuin.ac.jp}
• 关键词：hNEIL1 ; human NEIL1 ; hNTH1 ; human NTH1 ; BER ; base excision repair
• 刊名：Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
• 出版年：2012
• 期刊代码：115_00275107
• 类别：bio
• 出版时间：1 June, 2012
• 卷：734
• 期：1-2
• 页码：73-77
• 文件大小：494 K

摘要

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.