Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
J Cell Sci. 2013 Mar 15;126(Pt 6):1297-306. doi: 10.1242/jcs.096701.
DNA replication in eukaryotic cells initiates from multiple replication origins that are distributed throughout the genome. Coordinating the usage of these origins is crucial to ensure complete and timely replication of the entire genome precisely once in each cell cycle. Replication origins fire according to a cell-type-specific temporal programme, which is established in the G1 phase of each cell cycle. In response to conditions causing the slowing or stalling of DNA replication forks, the programme of origin firing is altered in two contrasting ways, depending on chromosomal context. First, inactive or 'dormant' replication origins in the vicinity of the stalled replication fork become activated and, second, the S phase checkpoint induces a global shutdown of further origin firing throughout the genome. Here, we review our current understanding on the role of dormant origins and the S phase checkpoint in the rescue of stalled forks and the completion of DNA replication in the presence of replicative stress.
真核细胞中的 DNA 复制从分布在整个基因组中的多个复制起点开始。协调这些起点的使用对于确保整个基因组在每个细胞周期中精确地复制一次是至关重要的。复制起点根据细胞类型特异性的时间程序启动，该程序在每个细胞周期的 G1 期建立。响应导致 DNA 复制叉减速或停滞的条件，根据染色体背景，起始的程序以两种相反的方式改变。首先，停滞复制叉附近的非活性或“休眠”复制起点被激活，其次，S 期检查点诱导整个基因组中进一步起始的全局关闭。在这里，我们回顾了我们目前对休眠起点和 S 期检查点在挽救停滞叉和完成复制压力下的 DNA 复制方面的作用的理解。
