Tan Kang Wei, Pham Tuan Minh, Furukohri Asako, Maki Hisaji, Akiyama Masahiro Tatsumi
Division of Systems Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Division of Systems Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan
Nucleic Acids Res. 2015 Feb 18;43(3):1714-25. doi: 10.1093/nar/gkv044. Epub 2015 Jan 27.
The SOS response is a DNA damage response pathway that serves as a general safeguard of genome integrity in bacteria. Extensive studies of the SOS response in Escherichia coli have contributed to establishing the key concepts of cellular responses to DNA damage. However, how the SOS response impacts on the dynamics of DNA replication fork movement remains unknown. We found that inducing the SOS response decreases the mean speed of individual replication forks by 30-50% in E. coli cells, leading to a 20-30% reduction in overall DNA synthesis. dinB and recA belong to a group of genes that are upregulated during the SOS response, and encode the highly conserved proteins DinB (also known as DNA polymerase IV) and RecA, which, respectively, specializes in translesion DNA synthesis and functions as the central recombination protein. Both genes were independently responsible for the SOS-dependent slowdown of replication fork progression. Furthermore, fork speed was reduced when each gene was ectopically expressed in SOS-uninduced cells to the levels at which they are expressed in SOS-induced cells. These results clearly indicate that the increased expression of dinB and recA performs a novel role in restraining the progression of an unperturbed replication fork during the SOS response.
SOS反应是一种DNA损伤反应途径，是细菌基因组完整性的一般保护机制。对大肠杆菌中SOS反应的广泛研究有助于确立细胞对DNA损伤反应的关键概念。然而，SOS反应如何影响DNA复制叉移动的动力学仍不清楚。我们发现，在大肠杆菌细胞中诱导SOS反应会使单个复制叉的平均速度降低30%-50%，导致总体DNA合成减少20%-30%。dinB和recA属于在SOS反应期间上调的一组基因，分别编码高度保守的蛋白质DinB（也称为DNA聚合酶IV）和RecA，其中DinB专门负责跨损伤DNA合成，RecA则作为核心重组蛋白发挥作用。这两个基因分别独立导致SOS依赖性的复制叉进展放缓。此外，当每个基因在未诱导SOS反应的细胞中异位表达至其在诱导SOS反应的细胞中的表达水平时，复制叉速度也会降低。这些结果清楚地表明，dinB和recA表达增加在SOS反应期间抑制未受干扰的复制叉进展中发挥了新作用。
