Structural basis of DNA replication origin recognition by human Orc6 protein binding with DNA.
Structural basis of DNA replication origin recognition by human Orc6 protein binding with DNA.
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人Orc6蛋白与DNA结合识别DNA复制起点的结构基础
DOI：
10.1093/nar/gkaa751
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发表时间：
2020-11-04
影响因子：
14.9
通讯作者：
Zhu G
中科院分区：
文献类型：
--
作者：
Xu N;You Y;Liu C;Balasov M;Lun LT;Geng Y;Fung CP;Miao H;Tian H;Choy TT;Shi X;Fan Z;Zhou B;Akhmetova K;Din RU;Yang H;Hao Q;Qian P;Chesnokov I;Zhu G
摘要作为一种DNA复制启动子，六亚单位起源识别复合体(ORC)定义了真核生物复制起始点的定位。ORC6亚基是ORC亚基中最小、保守程度最低的。它是DNA复制所必需的，对所有物种的生存都是必不可少的。后生动物中的ORC6与转录因子TFIIB具有结构上的同源性，并能独立结合DNA。在这里，我们报告了全长人类ORC6(HsOrc6)的单独和在与DNA的复合体中的溶液结构。我们进一步证明人ORC6由三个独立的结构域组成：N-末端、中间和C-末端(HsOrc6-N、HsOrc6-M和HsOrc6-C)。我们还鉴定了人ORC6的一个独特的DNA结合域，命名为HsOrc6-DBD。对结构的详细分析揭示了新的氨基酸簇对与DNA的相互作用非常重要。这些氨基酸的改变取消了ORC6的DNA结合能力，导致DNA复制水平降低。我们认为ORC6是人/后生动物ORC的DNA结合亚基，可能在起始点起到靶向、定位和组装功能ORC的作用。
Abstract The six-subunit origin recognition complex (ORC), a DNA replication initiator, defines the localization of the origins of replication in eukaryotes. The Orc6 subunit is the smallest and the least conserved among ORC subunits. It is required for DNA replication and essential for viability in all species. Orc6 in metazoans carries a structural homology with transcription factor TFIIB and can bind DNA on its own. Here, we report a solution structure of the full-length human Orc6 (HsOrc6) alone and in a complex with DNA. We further showed that human Orc6 is composed of three independent domains: N-terminal, middle and C-terminal (HsOrc6-N, HsOrc6-M and HsOrc6-C). We also identified a distinct DNA-binding domain of human Orc6, named as HsOrc6-DBD. The detailed analysis of the structure revealed novel amino acid clusters important for the interaction with DNA. Alterations of these amino acids abolish DNA-binding ability of Orc6 and result in reduced levels of DNA replication. We propose that Orc6 is a DNA-binding subunit of human/metazoan ORC and may play roles in targeting, positioning and assembling the functional ORC at the origins.
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影响因子：
3.3
作者：
Bell SP;Labib K
通讯作者：
Labib K
DOI：
10.1073/pnas.0911500106
发表时间：
2009-12-01
影响因子：
11.1
作者：
Evrin, Cecile;Clarke, Pippa;Speck, Christian
通讯作者：
Speck, Christian
影响因子：
3.3
作者：
Akhmetova K;Balasov M;Huijbregts RP;Chesnokov I
通讯作者：
Chesnokov I
DOI：
10.1073/pnas.1806315115
发表时间：
2018-06-26
影响因子：
11.1
作者：
Bleichert, Franziska;Leitner, Alexander;Berger, James M.
通讯作者：
Berger, James M.
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A