Family D DNA polymerase interacts with GINS to promote CMG-helicase in the archaeal replisome.
Family D DNA polymerase interacts with GINS to promote CMG-helicase in the archaeal replisome.
复制标题
家族D DNA聚合酶与GINS相互作用，促进古细菌复制体中的cmg -解旋酶。
DOI：
10.1093/nar/gkab799
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发表时间：
2022-04-22
影响因子：
14.9
通讯作者：
Ishino, Yoshizumi
中科院分区：
文献类型：
--
作者：
Oki, Keisuke;Nagata, Mariko;Yamagami, Takeshi;Numata, Tomoyuki;Ishino, Sonoko;Oyama, Takuji;Ishino, Yoshizumi
基因组DNA复制需要复制体组装。我们在这里显示的分子机制CMG（GAN-MCM-GINS）样解旋酶与家庭D DNA聚合酶（PolD）在Thermococcus kodakarensis合作。古细菌GINS含有两个Gins 51亚基，其C-末端结构域（Gins 51 C）与GAN相互作用。我们发现Gins 51 C还与PolD的DP 1亚基（DP 1 N）的N端结构域相互作用以连接GINS中的两个PolD。复制体中的两种复制酶应该分别负责前导链和滞后链的合成。DP 1 N-Gins 51 C-GAN三元复合物的晶体结构分析被提供以理解解旋酶和DNA聚合酶之间的连接的结构基础。定点突变分析支持从晶体结构获得的相互作用模式。此外，解旋酶和复制酶的组装在真核生物中也是保守的。PolD通过刺激CMG复合物的ATP酶活性来增强亲本链解旋。这是第一个证据的功能之间的联系复制酶和解旋酶在Escherichia。这些结果表明，PolD与CMG-解旋酶的直接相互作用对于同步链解旋和新生链合成是至关重要的，并且可能为复制叉的有效进展提供功能机制。
Genomic DNA replication requires replisome assembly. We show here the molecular mechanism by which CMG (GAN–MCM–GINS)-like helicase cooperates with the family D DNA polymerase (PolD) in Thermococcus kodakarensis. The archaeal GINS contains two Gins51 subunits, the C-terminal domain of which (Gins51C) interacts with GAN. We discovered that Gins51C also interacts with the N-terminal domain of PolD’s DP1 subunit (DP1N) to connect two PolDs in GINS. The two replicases in the replisome should be responsible for leading- and lagging-strand synthesis, respectively. Crystal structure analysis of the DP1N–Gins51C–GAN ternary complex was provided to understand the structural basis of the connection between the helicase and DNA polymerase. Site-directed mutagenesis analysis supported the interaction mode obtained from the crystal structure. Furthermore, the assembly of helicase and replicase identified in this study is also conserved in Eukarya. PolD enhances the parental strand unwinding via stimulation of ATPase activity of the CMG-complex. This is the first evidence of the functional connection between replicase and helicase in Archaea. These results suggest that the direct interaction of PolD with CMG-helicase is critical for synchronizing strand unwinding and nascent strand synthesis and possibly provide a functional machinery for the effective progression of the replication fork.
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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：
14.9
作者：
Pan M;Santangelo TJ;Li Z;Reeve JN;Kelman Z
通讯作者：
Kelman Z
DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
21.3
作者：
Gambus, A;Jones, RC;Labib, K
通讯作者：
Labib, K
影响因子：
2.2
作者：
Kushida, Takashi;Narumi, Issay;Higashibata, Hiroki
通讯作者：
Higashibata, Hiroki