Deaconescu Alexandra M, Chambers Anna L, Smith Abigail J, Nickels Bryce E, Hochschild Ann, Savery Nigel J, Darst Seth A
The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Cell. 2006 Feb 10;124(3):507-20. doi: 10.1016/j.cell.2005.11.045.
Coupling of transcription and DNA repair in bacteria is mediated by transcription-repair coupling factor (TRCF, the product of the mfd gene), which removes transcription elongation complexes stalled at DNA lesions and recruits the nucleotide excision repair machinery to the site. Here we describe the 3.2 A-resolution X-ray crystal structure of Escherichia coli TRCF. The structure consists of a compact arrangement of eight domains, including a translocation module similar to the SF2 ATPase RecG, and a region of structural similarity to UvrB. Biochemical and genetic experiments establish that another domain with structural similarity to the Tudor-like domain of the transcription elongation factor NusG plays a critical role in TRCF/RNA polymerase interactions. Comparison with the translocation module of RecG as well as other structural features indicate that TRCF function involves large-scale conformational changes. These data, along with a structural model for the interaction of TRCF with the transcription elongation complex, provide mechanistic insights into TRCF function.
细菌中转录与DNA修复的偶联由转录修复偶联因子（TRCF，mfd基因的产物）介导，该因子可去除在DNA损伤处停滞的转录延伸复合物，并将核苷酸切除修复机制招募至该位点。在此，我们描述了大肠杆菌TRCF的3.2埃分辨率X射线晶体结构。该结构由八个结构域紧密排列而成，包括一个类似于SF2 ATP酶RecG的转位模块，以及一个与UvrB结构相似的区域。生化和遗传学实验表明，另一个与转录延伸因子NusG的类Tudor结构域具有结构相似性的结构域在TRCF/RNA聚合酶相互作用中起关键作用。与RecG的转位模块以及其他结构特征的比较表明，TRCF的功能涉及大规模的构象变化。这些数据，连同TRCF与转录延伸复合物相互作用的结构模型，为TRCF的功能提供了机制上的见解。
