Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.
Mutat Res. 2012 Jun 1;734(1-2):73-7. doi: 10.1016/j.mrfmmm.2012.03.007. Epub 2012 Mar 23.
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.
碱基衍生物 2,2,4-三氨基-5(2H)-恶唑啉（Oz）是鸟嘌呤或 8-氧代-7,8-二氢鸟嘌呤的氧化产物，可导致 DNA 中的 G-C 颠换。人类 NEIL1（hNEIL1）和 NTH1（hNTH1）分别是两种原核碱基切除修复酶 FPG/NEI 和 NTH 的同源物。在这里，我们证明 hNEIL1 和 hNTH1 能够像 5-羟基尿嘧啶位点一样有效地切割 Oz 位点。因此，hNEIL1 和 hNTH1 可以修复 Oz 损伤。此外，这些酶的切口活性在很大程度上不依赖于与 Oz 相对的碱基；这一发现表明，从 Oz:G 和 Oz:A 碱基对中去除 Oz 可能会导致人类细胞中点突变率的增加。
