The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Genes (Basel). 2021 Nov 18;12(11):1812. doi: 10.3390/genes12111812.
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.
在每个细胞复制过程中，每个细胞中的整个基因组 DNA 必须被准确且快速地复制。考虑到这项任务的时间紧迫、需要多种蛋白质以及存在大量 DNA，因此 DNA 复制对细胞构成了严重的挑战。聚合酶和其他 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。对于维持这种协调，最重要的蛋白质之一是 PCNA。PCNA 是一种多功能蛋白，形成环绕 DNA 的三聚体环。它作为 DNA 聚合酶的持续因子发挥作用，并作为与 DNA 和染色质相互作用的不同蛋白质的着陆平台。因此，PCNA 是一个信号枢纽，影响 DNA 复制的速度和准确性、调节 DNA 损伤修复、控制复制过程中的染色质形成以及姐妹染色单体的正确分离。由于有如此多的重要作用，PCNA 在染色质上的募集和周转至关重要。三个不同的、保守的蛋白质复合物负责将 PCNA 加载/卸载到 DNA 上。复制因子 C（RFC）是负责在 S 期加载 PCNA 的典型复合物。Ctf18 和 Elg1（哺乳动物中的 ATAD5）蛋白形成类似于 RFC 的复合物，在细胞的核中有特定的功能。在这里，我们总结了我们目前对这些重要因素在酵母和哺乳动物中的作用的了解。
