Van Houten B
Department of Pathology, University of Vermont, Burlington 05405.
Microbiol Rev. 1990 Mar;54(1):18-51. doi: 10.1128/mr.54.1.18-51.1990.
One of the best-studied DNA repair pathways is nucleotide excision repair, a process consisting of DNA damage recognition, incision, excision, repair resynthesis, and DNA ligation. Escherichia coli has served as a model organism for the study of this process. Recently, many of the proteins that mediate E. coli nucleotide excision have been purified to homogeneity; this had led to a molecular description of this repair pathway. One of the key repair enzymes of this pathway is the UvrABC nuclease complex. The individual subunits of this enzyme cooperate in a complex series of partial reactions to bind to and incise the DNA near a damaged nucleotide. The UvrABC complex displays a remarkable substrate diversity. Defining the structural features of DNA lesions that provide the specificity for damage recognition by the UvrABC complex is of great importance, since it represents a unique form of protein-DNA interaction. Using a number of in vitro assays, researchers have been able to elucidate the action mechanism of the UvrABC nuclease complex. Current research is devoted to understanding how these complex events are mediated within the living cell.
研究得最为透彻的DNA修复途径之一是核苷酸切除修复,这一过程包括DNA损伤识别、切口形成、切除、修复再合成以及DNA连接。大肠杆菌一直作为研究这一过程的模式生物。最近,许多介导大肠杆菌核苷酸切除的蛋白质已被纯化至同质状态;这使得人们能够从分子层面描述这一修复途径。该途径的关键修复酶之一是UvrABC核酸酶复合体。这种酶的各个亚基通过一系列复杂的部分反应协同作用,结合并切割受损核苷酸附近的DNA。UvrABC复合体表现出显著的底物多样性。确定为UvrABC复合体提供损伤识别特异性的DNA损伤结构特征非常重要,因为这代表了一种独特的蛋白质-DNA相互作用形式。通过一些体外试验,研究人员已经能够阐明UvrABC核酸酶复合体的作用机制。目前的研究致力于了解这些复杂事件在活细胞内是如何介导的。