Brüning Jan-Gert, Howard Jamieson L, McGlynn Peter
Department of Biology, University of York, Wentworth Way, York YO10 5DD, United Kingdom.
Department of Biology, University of York, Wentworth Way, York YO10 5DD, United Kingdom.
J Mol Biol. 2014 Dec 12;426(24):3917-3928. doi: 10.1016/j.jmb.2014.10.001. Epub 2014 Oct 13.
Complete, accurate duplication of the genetic material is a prerequisite for successful cell division. Achieving this accuracy is challenging since there are many barriers to replication forks that may cause failure to complete genome duplication or result in possibly catastrophic corruption of the genetic code. One of the most important types of replicative barriers are proteins bound to the template DNA, especially transcription complexes. Removal of these barriers demands energy input not only to separate the DNA strands but also to disrupt multiple bonds between the protein and DNA. Replicative helicases that unwind the template DNA for polymerases at the fork can displace proteins bound to the template. However, even occasional failures in protein displacement by the replicative helicase could spell disaster. In such circumstances, failure to restart replication could result in incomplete genome duplication. Avoiding incomplete genome duplication via the repair and restart of blocked replication forks also challenges viability since the involvement of recombination enzymes is associated with the risk of genome rearrangements. Organisms have therefore evolved accessory replicative helicases that aid replication fork movement along protein-bound DNA. These helicases reduce the dangers associated with replication blockage by protein-DNA complexes, aiding clearance of blocks and resumption of replication by the same replisome thus circumventing the need for replication repair and restart. This review summarises recent work in bacteria and eukaryotes that has begun to delineate features of accessory replicative helicases and their importance in genome stability.
完整、准确地复制遗传物质是细胞成功分裂的前提条件。实现这种准确性具有挑战性，因为复制叉存在许多障碍，这些障碍可能导致无法完成基因组复制，或者可能导致遗传密码出现灾难性的破坏。最重要的复制障碍类型之一是与模板DNA结合的蛋白质，尤其是转录复合物。去除这些障碍不仅需要能量输入来分离DNA链，还需要破坏蛋白质与DNA之间的多个键。在复制叉处为聚合酶解开模板DNA的复制解旋酶可以取代与模板结合的蛋白质。然而，即使复制解旋酶偶尔无法取代蛋白质，也可能带来灾难。在这种情况下，无法重新启动复制可能导致基因组复制不完整。通过修复和重新启动受阻的复制叉来避免基因组复制不完整也对细胞活力构成挑战，因为重组酶的参与伴随着基因组重排的风险。因此，生物体进化出了辅助复制解旋酶，以帮助复制叉沿着与蛋白质结合的DNA移动。这些解旋酶降低了与蛋白质-DNA复合物导致的复制阻滞相关的危险，有助于清除阻滞并由同一个复制体重新启动复制，从而避免了复制修复和重新启动的需要。本综述总结了细菌和真核生物中最近的研究工作，这些工作开始描绘辅助复制解旋酶的特征及其在基因组稳定性中的重要性。
