Crowley D J, Hanawalt P C
Department of Biological Sciences, Stanford University, California 94305-5020, USA.
J Bacteriol. 1998 Jul;180(13):3345-52. doi: 10.1128/JB.180.13.3345-3352.1998.
Nucleotide excision repair (NER) is responsible for the removal of a variety of lesions from damaged DNA and proceeds through two subpathways, global repair and transcription-coupled repair. In Escherichia coli, both subpathways require UvrA and UvrB, which are induced following DNA damage as part of the SOS response. We found that elimination of the SOS response either genetically or by treatment with the transcription inhibitor rifampin reduced the efficiency of global repair of the major UV-induced lesion, the cyclobutane pyrimidine dimer (CPD), but had no effect on the global repair of 6-4 photoproducts. Mutants in which the SOS response was constitutively derepressed repaired CPDs more rapidly than did wild-type cells, and this rate was not affected by rifampin. Transcription-coupled repair of CPDs occurred in the absence of SOS induction but was undetectable when the response was expressed constitutively. These results suggest that damage-inducible synthesis of UvrA and UvrB is necessary for efficient repair of CPDs and that the levels of these proteins determine the rate of NER of UV photoproducts. We compare our findings with recent data from eukaryotic systems and suggest that damage-inducible stress responses are generally critical for efficient global repair of certain types of genomic damage.
核苷酸切除修复（NER）负责从受损DNA中去除多种损伤，并通过两条子途径进行，即全局修复和转录偶联修复。在大肠杆菌中，这两条子途径都需要UvrA和UvrB，它们在DNA损伤后作为SOS反应的一部分被诱导产生。我们发现，通过基因手段或用转录抑制剂利福平处理消除SOS反应，会降低主要紫外线诱导损伤——环丁烷嘧啶二聚体（CPD）的全局修复效率，但对6-4光产物的全局修复没有影响。SOS反应持续去抑制的突变体修复CPD的速度比野生型细胞更快，且这一速度不受利福平影响。CPD的转录偶联修复在没有SOS诱导的情况下发生，但在SOS反应持续表达时无法检测到。这些结果表明，UvrA和UvrB的损伤诱导合成对于CPD的有效修复是必要的，并且这些蛋白质的水平决定了紫外线光产物的核苷酸切除修复速率。我们将我们的发现与来自真核系统的最新数据进行了比较，并表明损伤诱导应激反应通常对于某些类型基因组损伤的有效全局修复至关重要。
