Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Cells. 2023 Nov 11;12(22):2607. doi: 10.3390/cells12222607.
Duplication of the genome requires the replication apparatus to overcome a variety of impediments, including covalent DNA adducts, the most challenging of which is on the leading template strand. Replisomes consist of two functional units, a helicase to unwind DNA and polymerases to synthesize it. The helicase is a multi-protein complex that encircles the leading template strand and makes the first contact with a leading strand adduct. The size of the channel in the helicase would appear to preclude transit by large adducts such as DNA: protein complexes (DPC). Here we discuss some of the extensively studied pathways that support replication restart after replisome encounters with leading template strand adducts. We also call attention to recent work that highlights the tolerance of the helicase for adducts ostensibly too large to pass through the central channel.
基因组的复制需要复制装置克服各种障碍，包括共价 DNA 加合物，其中最具挑战性的是在领头模板链上。复制体由两个功能单元组成，一个解旋酶来解开 DNA，聚合酶来合成 DNA。解旋酶是一个多蛋白复合物，环绕着领头模板链，并与领头链加合物首先接触。解旋酶通道的大小似乎排除了像 DNA: 蛋白质复合物 (DPC) 这样的大加合物的通过。在这里，我们讨论了一些广泛研究的途径，这些途径支持复制体与领头模板链加合物相遇后进行复制起始。我们还提请注意最近的工作，这些工作强调了解旋酶对加合物的耐受性，这些加合物大到显然无法通过中央通道。
