4dfc
Core UvrA/TRCF complexCore UvrA/TRCF complex
Structural highlights
Function[MFD_ECOLI] Couples transcription and DNA repair by recognizing RNA polymerase (RNAP) stalled at DNA lesions. Mediates ATP-dependent release of RNAP and its truncated transcript from the DNA, and recruitment of nucleotide excision repair machinery to the damaged site. Can also dissociate RNAP that is blocked by low concentration of nucleoside triphosphates or by physical obstruction, such as bound proteins. In addition, can rescue arrested complexes by promoting forward translocation. Has ATPase activity, which is required for removal of stalled RNAP, but seems to lack helicase activity. May act through a translocase activity that rewinds upstream DNA, leading either to translocation or to release of RNAP when the enzyme active site can not continue elongation.[1] [2] [3] [4] [5] Publication Abstract from PubMedTranscription-coupled DNA repair targets DNA lesions that block progression of elongating RNA polymerases. In bacteria, the transcription-repair coupling factor (TRCF; also known as Mfd) SF2 ATPase recognizes RNA polymerase stalled at a site of DNA damage, removes the enzyme from the DNA, and recruits the Uvr(A)BC nucleotide excision repair machinery via UvrA binding. Previous studies of TRCF revealed a molecular architecture incompatible with UvrA binding, leaving its recruitment mechanism unclear. Here, we examine the UvrA recognition determinants of TRCF using X-ray crystallography of a core TRCF-UvrA complex and probe the conformational flexibility of TRCF in the absence and presence of nucleotides using small-angle X-ray scattering. We demonstrate that the C-terminal domain of TRCF is inhibitory for UvrA binding, but not RNA polymerase release, and show that nucleotide binding induces concerted multidomain motions. Our studies suggest that autoinhibition of UvrA binding in TRCF may be relieved only upon engaging the DNA damage. Nucleotide excision repair (NER) machinery recruitment by the transcription-repair coupling factor involves unmasking of a conserved intramolecular interface.,Deaconescu AM, Sevostyanova A, Artsimovitch I, Grigorieff N Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3353-8. Epub 2012 Feb 13. PMID:22331906[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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