The Causes and Consequences of Topological Stress during DNA Replication.
The Causes and Consequences of Topological Stress during DNA Replication.
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DOI：
10.3390/genes7120134
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发表时间：
2016-12-21
期刊：
影响因子：
3.5
通讯作者：
Baxter J
中科院分区：
文献类型：
--
作者：
Keszthelyi A;Minchell NE;Baxter J
姐妹染色单体的忠实复制对于每次细胞分裂中基因组的完整性至关重要。复制机制必须克服每一轮复制中的许多困难，包括DNA拓扑应力。拓扑应力是由于 DNA 的双链螺旋性质而产生的。当链被拉开以进行复制时，双螺旋的缠绕也必须得到解决，否则会出现拓扑应力。 DNA 复制过程中遇到的特定染色体环境加剧了这一内在问题。终止过程中两个复制子的聚合、稳定的蛋白质-DNA 复合物的存在以及活跃的转录都会导致 DNA 复制受到拓扑应力。在这里，我们描述复制叉如何通过复制叉旋转和复制叉反转来响应拓扑应力。我们还讨论了真核生物中可能发生拓扑应激的基因组背景，重点关注转录的贡献。最后，我们描述了拓扑应力以及分叉对其的响应方式如何可能导致细胞中基因组的不稳定。
The faithful replication of sister chromatids is essential for genomic integrity in every cell division. The replication machinery must overcome numerous difficulties in every round of replication, including DNA topological stress. Topological stress arises due to the double-stranded helical nature of DNA. When the strands are pulled apart for replication to occur, the intertwining of the double helix must also be resolved or topological stress will arise. This intrinsic problem is exacerbated by specific chromosomal contexts encountered during DNA replication. The convergence of two replicons during termination, the presence of stable protein-DNA complexes and active transcription can all lead to topological stresses being imposed upon DNA replication. Here we describe how replication forks respond to topological stress by replication fork rotation and fork reversal. We also discuss the genomic contexts where topological stress is likely to occur in eukaryotes, focusing on the contribution of transcription. Finally, we describe how topological stress, and the ways forks respond to it, may contribute to genomic instability in cells.
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