7nvx
TFIIH in a post-translocated state (with ADP-BeF3)
Structural highlights
DiseaseERCC2_HUMAN Trichothiodystrophy;COFS syndrome;Xeroderma pigmentosum complementation group D. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionERCC2_HUMAN ATP-dependent 5'-3' DNA helicase, component of the core-TFIIH basal transcription factor. Involved in nucleotide excision repair (NER) of DNA by opening DNA around the damage, and in RNA transcription by RNA polymerase II by anchoring the CDK-activating kinase (CAK) complex, composed of CDK7, cyclin H and MAT1, to the core-TFIIH complex. Involved in the regulation of vitamin-D receptor activity. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation. Might have a role in aging process and could play a causative role in the generation of skin cancers.[1] [2] [3] [4] Publication Abstract from PubMedThe initiation of transcription is a focal point for the regulation of gene activity during mammalian cell differentiation and development. To initiate transcription, RNA polymerase II (Pol II) assembles with general transcription factors into a pre-initiation complex (PIC) that opens promoter DNA. Previous work provided the molecular architecture of the yeast(1-9) and human(10,11) PIC and a topological model for DNA opening by the general transcription factor TFIIH(12-14). Here we report the high-resolution cryo-electron microscopy structure of PIC comprising human general factors and Sus scrofa domesticus Pol II, which is 99.9% identical to human Pol II. We determine the structures of PIC with closed and opened promoter DNA at 2.5-2.8 A resolution, and resolve the structure of TFIIH at 2.9-4.0 A resolution. We capture the TFIIH translocase XPB in the pre- and post-translocation states, and show that XPB induces and propagates a DNA twist to initiate the opening of DNA approximately 30 base pairs downstream of the TATA box. We also provide evidence that DNA opening occurs in two steps and leads to the detachment of TFIIH from the core PIC, which may stop DNA twisting and enable RNA chain initiation. Structures of mammalian RNA polymerase II pre-initiation complexes.,Aibara S, Schilbach S, Cramer P Nature. 2021 Jun;594(7861):124-128. doi: 10.1038/s41586-021-03554-8. Epub 2021 , Apr 26. PMID:33902107[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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