Mueller Stefan H, Spenkelink Lisanne M, van Oijen Antoine M
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, 2522, Australia.
Illawarra Health & Medical Research Institute, Wollongong, New South Wales, 2522, Australia.
Biophys Rev. 2019 Jul 4;11(4):641-651. doi: 10.1007/s12551-019-00569-4.
DNA replication, or the copying of DNA, is a fundamental process to all life. The system of proteins that carries out replication, the replisome, encounters many roadblocks on its way. An inability of the replisome to properly overcome these roadblocks will negatively affect genomic integrity which in turn can lead to disease. Over the past decades, efforts by many researchers using a broad array of approaches have revealed roles for many different proteins during the initial response of the replisome upon encountering roadblocks. Here, we revisit what is known about DNA replication and the effect of roadblocks during DNA replication across different organisms. We also address how advances in single-molecule techniques have changed our view of the replisome from a highly stable machine with behavior dictated by deterministic principles to a dynamic system that is controlled by stochastic processes. We propose that these dynamics will play crucial roles in roadblock bypass. Further single-molecule studies of this bypass will, therefore, be essential to facilitate the in-depth investigation of multi-protein complexes that is necessary to understand complicated collisions on the DNA.
DNA复制，即DNA的拷贝，是所有生命的一个基本过程。执行复制的蛋白质系统，即复制体，在其复制过程中会遇到许多障碍。复制体无法妥善克服这些障碍将对基因组完整性产生负面影响，进而可能导致疾病。在过去几十年里，许多研究人员采用各种各样的方法进行研究，揭示了许多不同蛋白质在复制体遇到障碍时的初始反应过程中所起的作用。在此，我们重新审视关于DNA复制以及不同生物体DNA复制过程中障碍影响的已知信息。我们还探讨了单分子技术的进展如何改变了我们对复制体的看法，从一个行为由确定性原则支配的高度稳定的机器，转变为一个由随机过程控制的动态系统。我们提出，这些动态变化将在障碍绕过过程中发挥关键作用。因此，对这种绕过过程进行进一步的单分子研究，对于深入研究理解DNA上复杂碰撞所必需的多蛋白复合物至关重要。
