Division of RI Laboratory, Biomedical Research Center, Saitama Medical University, Japan.
Microbial Genetics Laboratory, National Institute of Genetics, Mishima, Japan.
FEBS Lett. 2019 Jul;593(13):1449-1458. doi: 10.1002/1873-3468.13481. Epub 2019 Jun 30.
When a cell divides prior to completion of DNA replication, serious DNA damage may occur. Thus, in addition to accuracy, the processivity of the replication forks is important. DNA synthesis at replication forks should be completed in time, and forks overcome aberrant structures on the template DNA, including damaged sites, using trans-lesion synthesis, occasionally introducing mutations. By contrast, the protein barrier built on the DNA is known to block the progression of replication forks at specific chromosomal loci. Such protein barriers avert any collision of replication and transcription machineries, or control the recombination of specific loci. The components and the mechanisms of action of protein barriers have been revealed mainly using genetic and biochemical techniques. In addition to proteins involved in replication fork pausing, the interaction of the replicative helicase and DNA polymerase is also essential for replication fork pausing. Here, we provide an overview of replication fork pausing at protein barriers.
当细胞在 DNA 复制完成之前分裂时，可能会发生严重的 DNA 损伤。因此，除了准确性之外，复制叉的连续性也很重要。复制叉上的 DNA 合成应该及时完成，并且叉利用跨损伤合成克服模板 DNA 上的异常结构，包括受损部位，偶尔会引入突变。相比之下，已知 DNA 上的蛋白质障碍会阻止特定染色体位置上的复制叉的前进。这种蛋白质障碍避免了复制和转录机制的任何碰撞，或者控制特定基因座的重组。蛋白质障碍的组成和作用机制主要是通过遗传和生化技术揭示的。除了参与复制叉暂停的蛋白质外，复制解旋酶和 DNA 聚合酶的相互作用对于复制叉暂停也是必不可少的。在这里，我们概述了蛋白质障碍处的复制叉暂停。
