Human endonuclease VIII-like (NEIL) proteins in the giant DNA Mimivirus
Human endonuclease VIII-like (NEIL) proteins in the giant DNA Mimivirus
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DOI：
10.1016/j.dnarep.2007.05.011
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发表时间：
2007-11-01
期刊：
影响因子：
3.8
通讯作者：
Wallace, Susan S.
中科院分区：
文献类型：
--
作者：
Bandaru, Viswanath;Zhao, Xiaobei;Wallace, Susan S.
核酸内切酶VIII(Nei)识别和修复碱基切除修复(BER)途径中的氧化嘧啶，广泛分布于原核生物和真核生物中。最近，我们和其他人在人类中发现了三个类似于大肠杆菌内切酶VIII(NeIL)蛋白的同源物。在这里，我们报告在感染棘阿米巴的巨型DNA病毒MimiVirus中鉴定出人类Neil同源物。对两个模拟病毒同源物MvNei1和MvNei2的鉴定表明，它们不仅与人Neil蛋白有序列同源性，而且具有底物特异性，即它们识别双链DNA和气泡底物中的氧化嘧啶，并具有5‘2-脱氧核糖-5-磷酸裂解酶(DRP裂解酶)活性。然而，与MvNeil和人类Neil蛋白不同的是，MvNei2优先在单链DNA形成产物中以不同的末端化学切割氧化的嘧啶。有趣的是，MvNei1的相反碱基特异性类似于人类Neil蛋白对嘧啶碱基的损伤，而它类似于大肠杆菌甲酰胺并嘧啶DNA糖基酶(FPG)对8-氧鸟嘌呤的氧化产物--瓜尼丁海因(Gh)。最后，MvNeil的DNA糖基酶活性需要在“无锌手指”基序中保守的精氨酸残基，这是以前在人类NEIL1中发现的。因此，MimiVirus代表了第一个携带底物特异性类似于人类Neil蛋白的氧化DNA糖基酶的病毒。根据与人类Neil同源物和新发现的细菌Neil同源物的序列同源性，我们预测MimiVirus可能通过宿主介导的从细菌或脊椎动物的侧向转移获得了DNA糖基酶。(C)2007 Elsevier B.V.保留所有权利。
Endonuclease VIII (Nei), which recognizes and repairs oxidized pyrimidines in the base excision repair (BER) pathway, is sparsely distributed among both the prokaryotes and eukaryotes. Recently, we and others identified three homologs of Escherichia coli endonuclease VIII-like (NEIL) proteins in humans. Here, we report identification of human NEIL homologs in Mimivirus, a giant DNA virus that infects Acanthamoeba. Characterization of the two mimiviral homologs, MvNei1 and MvNei2, showed that they share not only sequence homology but also substrate specificity with the human NEIL proteins, that is, they recognize oxidized pyrimidines in duplex DNA and in bubble substrates and as well show 5'2-deoxyribose-5-phosphate lyase (dRP lyase) activity. However, unlike MvNeil and the human NEIL proteins, MvNei2 preferentially cleaves oxidized pyrimidines in single stranded DNA forming products with a different end chemistry. Interestingly, opposite base specificity of MvNei1 resembles human NEIL proteins for pyrimidine base damages whereas it resembles E. coli formamidopyrimidine DNA glycosylase (Fpg) for guanidinohydantoin (Gh), an oxidation product of 8-oxoguanine. Finally, a conserved arginine residue in the "zinc-less finger" motif, previously identified in human NEIL1, is required for the DNA glycosylase activity of MvNeil. Thus, Mimivirus represents the first example of a virus to carry oxidative DNA glycosylases with substrate specificities that resemble human NEIL proteins. Based on the sequence homology to the human NEIL homologs and novel bacterial NEIL homologs identified here, we predict that Mimivirus may have acquired the DNA glycosylases through the host-mediated lateral transfer from either a bacterium or from vertebrates. (c) 2007 Elsevier B.V. All rights reserved.