Courcelle Charmain T, Landstrom Allison J, Anderson Brittany, Courcelle Justin
Department of Biology, Portland State University, Portland, Oregon, USA.
J Bacteriol. 2012 Aug;194(15):3977-86. doi: 10.1128/JB.00290-12. Epub 2012 May 25.
Following arrest by UV-induced DNA damage, replication is restored through a sequence of steps that involve partial resection of the nascent DNA by RecJ and RecQ, branch migration and processing of the fork DNA surrounding the lesion by RecA and RecF-O-R, and resumption of DNA synthesis once the blocking lesion has been repaired or bypassed. In vitro, the primosomal proteins (PriA, PriB, and PriC) and Rep are capable of initiating replication from synthetic DNA fork structures, and they have been proposed to catalyze these events when replication is disrupted by certain impediments in vivo. Here, we characterized the role that PriA, PriB, PriC, and Rep have in processing and restoring replication forks following arrest by UV-induced DNA damage. We show that the partial degradation and processing of the arrested replication fork occurs normally in both rep and primosome mutants. In each mutant, the nascent degradation ceases and DNA synthesis initially resumes in a timely manner, but the recovery then stalls in the absence of PriA, PriB, or Rep. The results demonstrate a role for the primosome and Rep helicase in overcoming replication forks arrested by UV-induced damage in vivo and suggest that these proteins are required for the stability and efficiency of the replisome when DNA synthesis resumes but not to initiate de novo replication downstream of the lesion.
在紫外线诱导的DNA损伤导致复制停滞之后,通过一系列步骤恢复复制,这些步骤包括RecJ和RecQ对新生DNA进行部分切除,RecA和RecF - O - R对损伤周围的叉状DNA进行分支迁移和加工,以及一旦阻断损伤被修复或绕过便恢复DNA合成。在体外,引发体蛋白(PriA、PriB和PriC)和Rep能够从合成的DNA叉状结构起始复制,并且有人提出当体内复制因某些障碍而中断时,它们可催化这些事件。在此,我们表征了PriA、PriB、PriC和Rep在紫外线诱导的DNA损伤导致复制停滞之后对复制叉的加工和恢复中所起的作用。我们表明,在rep和引发体突变体中,停滞的复制叉的部分降解和加工均正常发生。在每个突变体中,新生链的降解停止,DNA合成最初及时恢复,但在没有PriA、PriB或Rep的情况下,恢复随后停滞。结果证明引发体和Rep解旋酶在体内克服紫外线诱导损伤导致的复制叉停滞中发挥作用,并表明当DNA合成恢复时,这些蛋白质对于复制体的稳定性和效率是必需的,但对于损伤下游的从头复制起始并非必需。