The Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, U.S.A.
Institute for Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
Biochem Soc Trans. 2020 Jun 30;48(3):823-836. doi: 10.1042/BST20190363.
DNA replication is a complex process that needs to be executed accurately before cell division in order to maintain genome integrity. DNA replication is divided into three main stages: initiation, elongation and termination. One of the key events during initiation is the assembly of the replicative helicase at origins of replication, and this mechanism has been very well described over the last decades. In the last six years however, researchers have also focused on deciphering the molecular mechanisms underlying the disassembly of the replicative helicase during termination. Similar to replisome assembly, the mechanism of replisome disassembly is strictly regulated and well conserved throughout evolution, although its complexity increases in higher eukaryotes. While budding yeast rely on just one pathway for replisome disassembly in S phase, higher eukaryotes evolved an additional mitotic pathway over and above the default S phase specific pathway. Moreover, replisome disassembly has been recently found to be a key event prior to the repair of certain DNA lesions, such as under-replicated DNA in mitosis and inter-strand cross-links (ICLs) in S phase. Although replisome disassembly in human cells has not been characterised yet, they possess all of the factors involved in these pathways in model organisms, and de-regulation of many of them are known to contribute to tumorigenesis and other pathological conditions.
DNA 复制是一个复杂的过程，需要在细胞分裂前准确执行，以维持基因组的完整性。DNA 复制分为三个主要阶段：起始、延伸和终止。起始过程中的一个关键事件是复制起始点处的复制解旋酶的组装，在过去几十年中，该机制已得到很好的描述。然而，在过去的六年中，研究人员还专注于破译终止过程中复制解旋酶解体的分子机制。与复制体组装类似，复制体解体的机制在进化过程中受到严格调控且高度保守，尽管在高等真核生物中其复杂性增加。虽然芽殖酵母在 S 期仅依赖一种途径进行复制体解体，但高等真核生物在默认的 S 期特异性途径之外还进化出了一种有丝分裂途径。此外，最近发现复制体解体是修复某些 DNA 损伤（如有丝分裂中复制不足的 DNA 和 S 期的链间交联 (ICL)）之前的关键事件。尽管尚未对人类细胞中的复制体解体进行表征，但它们在模式生物中拥有参与这些途径的所有因素，并且已知许多因素的失调会导致肿瘤发生和其他病理状况。
