Atomic structure of an archaeal GAN suggests its dual roles as an exonuclease in DNA repair and a CMG component in DNA replication.
Atomic structure of an archaeal GAN suggests its dual roles as an exonuclease in DNA repair and a CMG component in DNA replication.
复制标题
DOI：
10.1093/nar/gkw789
复制
发表时间：
2016-11-02
影响因子：
14.9
通讯作者：
Ishino Y
中科院分区：
文献类型：
--
作者：
Oyama T;Ishino S;Shirai T;Yamagami T;Nagata M;Ogino H;Kusunoki M;Ishino Y
在真核生物DNA复制起始过程中，六聚体MCM（mini-chromosome maintenance）将模板双链DNA解旋形成复制叉。MCM被两种蛋白质Cdc 45和GINS激活，这两种蛋白质与MCM核心一起构成“CMG”无windosome复合物。古细菌DNA复制系统与真核生物非常相似，但从结构的角度来看，关于DNA解旋机制的知识有限。在这里，我们描述了古菌GAN（GINS相关核酸酶）的晶体结构，从热球菌kodakaraensis，真核Cdc 45的同源物，在两个自由形式和复杂的同源Gins 51亚基（Gins 51 C）的C-末端结构域。这第一个古菌GAN结构表现出细菌RecJ和真核Cdc 45之间独特的“杂交”结构。GAN具有保守的DHH和DHH 1结构域，负责外切核酸酶活性，以及插入的CID（CMG相互作用结构域）样结构域，结构上与Cdc 45相似，表明其作为DNA修复中的外切核酸酶和DNA复制中的CMG组分的双重作用。GAN-Gins 51 C复合物与GINS四聚体的结构比较表明，GINS使用移动的Gins 51 C作为钩来结合GAN以形成CMG。
In eukaryotic DNA replication initiation, hexameric MCM (mini-chromosome maintenance) unwinds the template double-stranded DNA to form the replication fork. MCM is activated by two proteins, Cdc45 and GINS, which constitute the ‘CMG’ unwindosome complex together with the MCM core. The archaeal DNA replication system is quite similar to that of eukaryotes, but only limited knowledge about the DNA unwinding mechanism is available, from a structural point of view. Here, we describe the crystal structure of an archaeal GAN (GINS-associated nuclease) from Thermococcus kodakaraensis, the homolog of eukaryotic Cdc45, in both the free form and the complex with the C-terminal domain of the cognate Gins51 subunit (Gins51C). This first archaeal GAN structure exhibits a unique, ‘hybrid’ structure between the bacterial RecJ and the eukaryotic Cdc45. GAN possesses the conserved DHH and DHH1 domains responsible for the exonuclease activity, and an inserted CID (CMG interacting domain)-like domain structurally comparable to that in Cdc45, suggesting its dual roles as an exonuclease in DNA repair and a CMG component in DNA replication. A structural comparison of the GAN–Gins51C complex with the GINS tetramer suggests that GINS uses the mobile Gins51C as a hook to bind GAN for CMG formation.
登录
查看更多内容
影响因子：
7.7
作者：
Cheng K;Xu H;Chen X;Wang L;Tian B;Zhao Y;Hua Y
通讯作者：
Hua Y
影响因子：
21.3
作者：
Gambus, A;Jones, RC;Labib, K
通讯作者：
Labib, K
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
14.9
作者：
Li Z;Pan M;Santangelo TJ;Chemnitz W;Yuan W;Edwards JL;Hurwitz J;Reeve JN;Kelman Z
通讯作者：
Kelman Z
DOI：
10.1073/pnas.0808037105
发表时间：
2008-12-23
影响因子：
11.1
作者：
Brewster, Aaron S.;Wang, Ganggang;Chen, Xiaojiang S.
通讯作者：
Chen, Xiaojiang S.