Two paths to let the replisome go.
Two paths to let the replisome go.
复制标题
DOI：
10.1038/cdd.2017.75
复制
发表时间：
2017-07
影响因子：
12.4
通讯作者：
Guardavaccaro D
中科院分区：
文献类型：
--
作者：
D'Angiolella V;Guardavaccaro D
准确的 DNA 复制对于基因组维护至关重要。最近的两份报告揭示了控制高等真核生物中 DNA 复制终止阶段的新分子机制，并确定了 CRL2LRR1 泛素连接酶和 p97 分离酶在从染色质卸载复制体中的关键作用。真核 DNA 复制可分为三个不同的步骤。在许可期间，复制前复合物 (pre-RC) 在细胞周期 G1 期的 DNA 复制起点处组装。随后在 G1-S 相变时开始复制，此时 CDK（细胞周期蛋白依赖性激酶）和 DDK（DBF4 依赖性激酶）促进 GINS 复合物和 CDC45 的募集，以组装启动双向 DNA 合成的活性 CMG (Cdc45-MCM-GINS) 解旋酶。 1 DNA 合成完成后，CMG 解旋酶在复制终止过程中被分解并从染色质中卸载。大量研究表明，DNA 复制的早期阶段受到泛素化的调节。例如，E3 泛素连接酶复合物 cullin-RING ligase-1 (CRL1) 和 cullin-RING ligase-4 (CRL4) 通过靶向前 RC 成分进行蛋白酶体降解，防止再复制和基因组不稳定的发生（Truong 等人综述 2）。 Cullin-RING 连接酶 (CRL) 构成超过 200 个模块 E3 的蛋白质家族，并由含有不同 cullin 的八个不同亚家族组成，即 CUL1、CUL2、CUL3、CUL4A、CUL4B、CUL5、CUL7 和 CUL9。 3 Cullins 作为分子支架组装不同的复杂亚基，即环指蛋白（RBX1 或 RBX2），它与泛素结合酶、衔接蛋白和许多底物受体亚基之一相互作用。 CRL 的活性主要在底物招募水平上进行控制。底物受体亚基对靶蛋白的直接识别及其向核心 CRL 平台的招募实际上是根据特定刺激进行调节的。此外，所有 CRL 都是通过泛素样蛋白 Nedd8 与 cullin 亚基共价连接而被激活。最近的研究表明，DNA 复制的最后阶段，即复制终止，也是由 CRL 介导的泛素化控制的。 4, 5 在芽殖酵母中，
Accurate DNA replication is essential for genome maintenance. Two recent reports have uncovered new molecular mechanisms controlling the termination phase of DNA replication in higher eukaryotes and established crucial roles for the CRL2LRR1 ubiquitin ligase and the p97 segregase in replisome unloading from chromatin. Eukaryotic DNA replication can be divided into three distinct steps. During licensing, pre-replication complexes (pre-RCs) assemble at DNA replication origins in the G1 phase of the cell cycle. This is followed by replication initiation at the G1-S phase transition, when CDKs (cyclin-dependent kinases) and DDKs (DBF4-dependent kinases) promote the recruitment of the GINS complex and CDC45 to assemble an active CMG (Cdc45-MCM-GINS) helicase that initiates bidirectional DNA synthesis. 1 When DNA synthesis is completed, the CMG helicase is disassembled and unloaded from chromatin during replication termination.A multitude of studies have demonstrated that the early phases of DNA replication are regulated by ubiquitylation. For instance, the E3 ubiquitin ligase complexes cullin-RING ligase-1 (CRL1) and cullin-RING ligase-4 (CRL4) prevent re-replication and the occurrence of genome instability by targeting pre-RC components for proteasomal degradation (reviewed in Truong et al. 2). Cullin-RING ligases (CRLs) constitute a protein family of> 200 modular E3s and are composed of eight distinct subfamilies containing different cullins, namely CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7 and CUL9. 3 Cullins work as molecular scaffolds assembling the different complex subunits, that is, a RING-finger protein (RBX1 or RBX2), which interacts with the ubiquitin-conjugating enzyme, an adaptor protein and one of many substrate-receptor subunits. The activity of CRLs is primarily controlled at the level of substrate recruitment. The direct recognition of the target protein by the substratereceptor subunit and its recruitment to the core CRL platform are in fact regulated in response to specific stimuli. Moreover, all CRLs are activated through the covalent attachment of the ubiquitin-like protein Nedd8 to the cullin subunit. It has been recently shown that also the final phase of DNA replication, that is, replication termination, is controlled by CRL-mediated ubiquitylation. 4, 5 In budding yeast, the
登录
查看更多内容
DOI：
10.1098/rstb.2011.0073
发表时间：
2011-12-27
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Diffley JF
通讯作者：
Diffley JF
影响因子：
10.5
作者：
Dewar JM;Low E;Mann M;Räschle M;Walter JC
通讯作者：
Walter JC
DOI：
10.1126/science.1253596
发表时间：
2014-10-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Maric M;Maculins T;De Piccoli G;Labib K
通讯作者：
Labib K
影响因子：
4.6
作者：
Merlet, Jorge;Burger, Julien;Pintard, Lionel
通讯作者：
Pintard, Lionel
影响因子：
21.3
作者：
Sonneville R;Moreno SP;Knebel A;Johnson C;Hastie CJ;Gartner A;Gambus A;Labib K
通讯作者：
Labib K