Andreassen Paul R, Ho Gary P H, D'Andrea Alan D
Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Carcinogenesis. 2006 May;27(5):883-92. doi: 10.1093/carcin/bgi319. Epub 2006 Feb 20.
The cellular response to DNA damage is composed of cell cycle checkpoint and DNA repair mechanisms that serve to ensure proper replication of the genome prior to cell division. The function of the DNA damage response during DNA replication in S-phase is critical to this process. Recent evidence has suggested a number of interrelationships of DNA replication and cellular DNA damage responses. These include S-phase checkpoints which suppress replication initiation or elongation in response to DNA damage. Also, many components of the DNA damage response are required either for the stabilization of, or for restarting, stalled replication forks. Further, translesion synthesis permits DNA replication to proceed in the presence of DNA damage and can be coordinated with subsequent repair by homologous recombination (HR). Finally, cohesion of sister chromatids is established coincident with DNA replication and is required for subsequent DNA repair by homologous recombination. Here we review these processes, all of which occur at, or are related to, the advancing replication fork. We speculate that these multiple interdependencies of DNA replication and DNA damage responses integrate the many steps necessary to ensure accurate duplication of the genome.
细胞对DNA损伤的反应由细胞周期检查点和DNA修复机制组成，这些机制有助于确保基因组在细胞分裂前正确复制。S期DNA复制过程中DNA损伤反应的功能对这一过程至关重要。最近的证据表明了DNA复制与细胞DNA损伤反应之间的一些相互关系。这些包括S期检查点，其响应DNA损伤而抑制复制起始或延伸。此外，DNA损伤反应的许多成分对于停滞复制叉的稳定或重启是必需的。此外，跨损伤合成允许DNA复制在存在DNA损伤的情况下进行，并且可以与随后的同源重组（HR）修复相协调。最后，姐妹染色单体的黏连在DNA复制时建立，并且是随后通过同源重组进行DNA修复所必需的。在这里，我们综述这些过程，所有这些过程都发生在前进的复制叉处或与之相关。我们推测，DNA复制和DNA损伤反应的这些多重相互依赖整合了确保基因组准确复制所需的许多步骤。
