2ja8
CPD lesion containing RNA Polymerase II elongation complex D
Structural highlights
FunctionRPB2_YEAST DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest component of RNA polymerases II which synthesizes mRNA precursors and many functional non-coding RNAs. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. During a transcription cycle, Pol II, general transcription factors and the Mediator complex assemble as the preinitiation complex (PIC) at the promoter. 11-15 base pairs of DNA surrounding the transcription start site are melted and the single stranded DNA template strand of the promoter is positioned deeply within the central active site cleft of Pol II to form the open complex. After synthesis of about 30 bases of RNA, Pol II releases its contacts with the core promoter and the rest of the transcription machinery (promoter clearance) and enters the stage of transcription elongation in which it moves on the template as the transcript elongates. Pol II appears to oscillate between inactive and active conformations at each step of nucleotide addition. Pol II is composed of mobile elements that move relative to each other. The core element with the central large cleft comprises RPB3, RBP10, RPB11, RPB12 and regions of RPB1 and RPB2 forming the active center. The clamp element (portions of RPB1, RPB2 and RPB3) is connected to the core through a set of flexible switches and moves to open and close the cleft. The cleft is surrounded by jaws: an upper jaw formed by portions of RBP1, RPB2 and RPB9, and a lower jaw. The jaws are thought to grab the incoming DNA template. The fork loop 1 (RPB2) interacts with the RNA-DNA hybrid, possibly stabilizing it. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCells use transcription-coupled repair (TCR) to efficiently eliminate DNA lesions such as ultraviolet light-induced cyclobutane pyrimidine dimers (CPDs). Here we present the structure-based mechanism for the first step in eukaryotic TCR, CPD-induced stalling of RNA polymerase (Pol) II. A CPD in the transcribed strand slowly passes a translocation barrier and enters the polymerase active site. The CPD 5'-thymine then directs uridine misincorporation into messenger RNA, which blocks translocation. Artificial replacement of the uridine by adenosine enables CPD bypass; thus, Pol II stalling requires CPD-directed misincorporation. In the stalled complex, the lesion is inaccessible, and the polymerase conformation is unchanged. This is consistent with nonallosteric recruitment of repair factors and excision of a lesion-containing DNA fragment in the presence of Pol II. CPD damage recognition by transcribing RNA polymerase II.,Brueckner F, Hennecke U, Carell T, Cramer P Science. 2007 Feb 9;315(5813):859-62. PMID:17290000[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
