Control of Genome Integrity by RFC Complexes; Conductors of PCNA Loading onto and Unloading from Chromatin during DNA Replication.
Control of Genome Integrity by RFC Complexes; Conductors of PCNA Loading onto and Unloading from Chromatin during DNA Replication.
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DOI：
10.3390/genes8020052
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发表时间：
2017-01-26
期刊：
影响因子：
3.5
通讯作者：
Nishitani H
中科院分区：
文献类型：
--
作者：
Shiomi Y;Nishitani H
在细胞分裂过程中，基因组的完整性是通过S期DNA的忠实复制和有丝分裂的精确分离来维持的。许多与DNA复制相关的DNA代谢事件也在整个细胞周期中受到调节。在真核生物中，DNA滑动钳，增殖细胞核抗原（PCNA），作为DNA聚合酶的持续合成因子作用于染色质。自发现以来，已经确定了许多其他PCNA结合伴侣在DNA复制，修复，重组，染色质重塑，凝聚力和细胞周期进程中的蛋白水解过程中发挥作用。PCNA不仅招募参与这些事件的蛋白质，而且还积极控制它们作为染色质组装的功能。因此，控制PCNA加载到染色质上是各种复制偶联反应的基础。PCNA通过装载复制因子C（RFC）的复合物装载到染色质上。RFC 1-RFC和Ctf 18-RFC基本上都起PCNA加载器的作用。另一方面，在DNA合成后，PCNA必须通过Elg 1-RFC从染色质中去除。RFC复合体的功能缺陷导致染色体异常。在这篇综述中，我们总结了RFC复合物之间的结构和功能关系，并描述了如何调节PCNA加载/卸载RFC复合物有助于维持基因组的完整性。
During cell division, genome integrity is maintained by faithful DNA replication during S phase, followed by accurate segregation in mitosis. Many DNA metabolic events linked with DNA replication are also regulated throughout the cell cycle. In eukaryotes, the DNA sliding clamp, proliferating cell nuclear antigen (PCNA), acts on chromatin as a processivity factor for DNA polymerases. Since its discovery, many other PCNA binding partners have been identified that function during DNA replication, repair, recombination, chromatin remodeling, cohesion, and proteolysis in cell-cycle progression. PCNA not only recruits the proteins involved in such events, but it also actively controls their function as chromatin assembles. Therefore, control of PCNA-loading onto chromatin is fundamental for various replication-coupled reactions. PCNA is loaded onto chromatin by PCNA-loading replication factor C (RFC) complexes. Both RFC1-RFC and Ctf18-RFC fundamentally function as PCNA loaders. On the other hand, after DNA synthesis, PCNA must be removed from chromatin by Elg1-RFC. Functional defects in RFC complexes lead to chromosomal abnormalities. In this review, we summarize the structural and functional relationships among RFC complexes, and describe how the regulation of PCNA loading/unloading by RFC complexes contributes to maintaining genome integrity.