PCNA Loaders and Unloaders-One Ring That Rules Them All.

PCNA Loaders and Unloaders-One Ring That Rules Them All.
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DOI:
10.3390/genes12111812
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发表时间:
2021-11-18
期刊:
影响因子:
3.5
通讯作者:
Kupiec M
Kupiec M
中科院分区:
生物学3区
文献类型:
--
作者:
Arbel M;Choudhary K;Tfilin O;Kupiec M

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在每次细胞复制过程中,每个细胞中的全部基因组DNA都必须准确而快速地复制。考虑到完成这项任务所需的时间很短,需要许多蛋白质,以及存在的令人生畏的DNA数量,DNA复制对细胞构成了严峻的挑战。聚合酶与其他DNA和染色质相互作用蛋白之间的高度协调对于完成这项任务至关重要。维持这种协调的最重要的蛋白质之一是PCNA。PCNA是一种多任务蛋白质,它形成一个围绕DNA的三聚体环。它作为DNA聚合酶的加工因子,并作为不同蛋白质与DNA和染色质相互作用的着陆平台。因此,PCNA是影响DNA复制速率和准确性、调节DNA损伤修复、控制复制过程中染色质形成以及姐妹染色单体适当分离的信号中枢。染色质上的PCNA招募和转换具有如此多的重要作用,是至关重要的。三种不同的、保守的蛋白质复合物负责将PCNA装载/卸载到DNA上。复制因子C (RFC)是在s期负责装载PCNA的典型复合体。Ctf18和Elg1(哺乳动物中的ATAD5)蛋白形成类似于RFC的复合物,在细胞核中具有特殊功能。在这里,我们总结了目前关于这些重要因素在酵母和哺乳动物中的作用的知识。
During each cell duplication, the entirety of the genomic DNA in every cell must be accurately and quickly copied. Given the short time available for the chore, the requirement of many proteins, and the daunting amount of DNA present, DNA replication poses a serious challenge to the cell. A high level of coordination between polymerases and other DNA and chromatin-interacting proteins is vital to complete this task. One of the most important proteins for maintaining such coordination is PCNA. PCNA is a multitasking protein that forms a homotrimeric ring that encircles the DNA. It serves as a processivity factor for DNA polymerases and acts as a landing platform for different proteins interacting with DNA and chromatin. Therefore, PCNA is a signaling hub that influences the rate and accuracy of DNA replication, regulates DNA damage repair, controls chromatin formation during the replication, and the proper segregation of the sister chromatids. With so many essential roles, PCNA recruitment and turnover on the chromatin is of utmost importance. Three different, conserved protein complexes are in charge of loading/unloading PCNA onto DNA. Replication factor C (RFC) is the canonical complex in charge of loading PCNA during the S-phase. The Ctf18 and Elg1 (ATAD5 in mammalian) proteins form complexes similar to RFC, with particular functions in the cell’s nucleus. Here we summarize our current knowledge about the roles of these important factors in yeast and mammals.
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