SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia.
FEBS Lett. 2010 Apr 16;584(8):1553-7. doi: 10.1016/j.febslet.2010.03.009. Epub 2010 Mar 7.
8-oxo-7,8-dihydroadenine (8-oxoAde) is a major product of adenine modification by reactive oxygen species. So far, only one mammalian DNA glycosylase, 8-oxoguanine-DNA-glycosylase 1 (OGG1), has been shown to excise 8-oxoAde, exclusively from pairs with Cyt. We have found that endonuclease VIII-like protein 1 (NEIL1), a mammalian homolog of bacterial endonuclease VIII, can efficiently remove 8-oxoAde from 8-oxoAde:Cyt pairs but not from other contexts. In an in vitro reconstituted system, reactions containing OGG1 produced a fully repaired product, whereas NEIL1 caused an abortive initiation of repair, stopping after 8-oxoAde removal and DNA strand cleavage. This block was partially relieved by polynucleotide kinase/3'-phosphatase. Thus, two alternative routes of 8-oxoAde repair may exist in mammals.
8-氧代-7,8-二氢腺嘌呤（8-氧代腺嘌呤）是活性氧物种修饰腺嘌呤的主要产物。到目前为止，只有一种哺乳动物 DNA 糖苷酶，8-氧代鸟嘌呤-DNA-糖苷酶 1（OGG1），被证明可以从 Cyt 配对中专门切除 8-氧代腺嘌呤。我们发现，内切核酸酶 VIII 样蛋白 1（NEIL1），一种细菌内切核酸酶 VIII 的哺乳动物同源物，可以有效地从 8-氧代腺嘌呤：Cyt 对中去除 8-氧代腺嘌呤，但不能从其他情况下去除。在体外重建的系统中，含有 OGG1 的反应产生了完全修复的产物，而 NEIL1 导致修复的无效起始，在 8-氧代腺嘌呤去除和 DNA 链断裂后停止。多核苷酸激酶/3'-磷酸酶部分缓解了这种阻断。因此，8-氧代腺嘌呤的修复可能存在两种替代途径。
