Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB.
Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB.
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DOI：
10.1186/1471-2164-4-48
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发表时间：
2003-12-10
期刊：
影响因子：
4.4
通讯作者：
Bujnicki JM
中科院分区：
文献类型：
--
作者：
Kurowski MA;Bhagwat AS;Papaj G;Bujnicki JM
生物化学和生物信息学分析的结合导致了氧化去甲基化的发现-一种由大肠杆菌AlkB蛋白及其两种人类同源物hABH 2和hABH 3催化的新型DNA修复机制。这一发现是基于Aravind和Koonin的预测，即AlkB是2 OG-Fe 2+加氧酶超家族的成员。在这篇文章中，我们报告的（2 OG-Fe 2+）加氧酶超家族的五个人类成员的鉴定和序列分析，这里指定为hABH 4通过hABH 8。在任何数据库中，这些实验未表征和注释不佳的基因与AlkB家族无关，但在此预测与AlkB家族（特别是与将hABH 2和hABH 3分组在一起的谱系）而不是与任何其他加氧酶家族在遗传学和功能上相关。我们的分析揭示了ABH基因重复在脊椎动物基因组进化中的历史。我们推测hABH 4-8可能是hABH 1 -3的备用酶，或者可能编码新的DNA或RNA修复活性。例如，还没有描述可以使DNA中的N3-甲基嘌呤或N7-甲基嘌呤脱烷基化的酶。我们的分析将指导这些新的人类推定的DNA修复酶的实验确认。
Combination of biochemical and bioinformatic analyses led to the discovery of oxidative demethylation – a novel DNA repair mechanism catalyzed by the Escherichia coli AlkB protein and its two human homologs, hABH2 and hABH3. This discovery was based on the prediction made by Aravind and Koonin that AlkB is a member of the 2OG-Fe2+ oxygenase superfamily. In this article, we report identification and sequence analysis of five human members of the (2OG-Fe2+) oxygenase superfamily designated here as hABH4 through hABH8. These experimentally uncharacterized and poorly annotated genes were not associated with the AlkB family in any database, but are predicted here to be phylogenetically and functionally related to the AlkB family (and specifically to the lineage that groups together hABH2 and hABH3) rather than to any other oxygenase family. Our analysis reveals the history of ABH gene duplications in the evolution of vertebrate genomes. We hypothesize that hABH 4–8 could either be back-up enzymes for hABH1-3 or may code for novel DNA or RNA repair activities. For example, enzymes that can dealkylate N3-methylpurines or N7-methylpurines in DNA have not been described. Our analysis will guide experimental confirmation of these novel human putative DNA repair enzymes.
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影响因子：
14.9
作者：
Tatusov, RL;Natale, DA;Koonin, EV
通讯作者：
Koonin, EV
影响因子：
1.4
作者：
Eisen, JA;Wu, M
通讯作者：
Wu, M
影响因子：
3.9
作者：
SAITOU, N
通讯作者：
SAITOU, N
影响因子：
10.7
作者：
SAITOU, N;NEI, M
通讯作者：
NEI, M
影响因子：
5.8
作者：
Shimodaira, H;Hasegawa, M
通讯作者：
Hasegawa, M