5xv8
From Proteopedia
Solution structure of the complex between UVSSA acidic region and TFIIH p62 PH domain
Structural highlights
Disease[UVSSA_HUMAN] UV-sensitive syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function[UVSSA_HUMAN] Factor involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage. TC-NER allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Acts by promoting stabilization of ERCC6 by recruiting deubiquitinating enzyme USP7 to TC-NER complexes, preventing UV-induced degradation of ERCC6 by the proteasome. Interacts with the elongating form of RNA polymerase II (RNA pol IIo) and facilitates its ubiquitination at UV damage sites, leading to promote RNA pol IIo backtracking to allow access to the nucleotide excision repair machinery. Not involved in processing oxidative damage.[1] [2] [3] [TF2H1_HUMAN] Component of the core-TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. Publication Abstract from PubMedNucleotide excision repair is initiated by two different damage recognition subpathways, global genome repair (GGR) and transcription-coupled repair (TCR). In GGR, XPC detects DNA lesions and recruits TFIIH via interaction with the pleckstrin homology (PH) domain of TFIIH subunit p62. In TCR, an elongating form of RNA Polymerase II detects a lesion on the transcribed strand and recruits TFIIH by an unknown mechanism. Here, we found that the TCR initiation factor UVSSA forms a stable complex with the PH domain of p62 via a short acidic string in the central region of UVSSA, and determined the complex structure by NMR. The acidic string of UVSSA binds strongly to the basic groove of the PH domain by inserting Phe408 and Val411 into two pockets, highly resembling the interaction mechanism of XPC with p62. Mutational binding analysis validated the structure and identified residues crucial for binding. TCR activity was markedly diminished in UVSSA -deficient cells expressing UVSSA mutated at Phe408 or Val411. Thus, a common TFIIH recruitment mechanism is shared by UVSSA in TCR and XPC in GGR. Common TFIIH recruitment mechanism in global genome and transcription-coupled repair subpathways.,Okuda M, Nakazawa Y, Guo C, Ogi T, Nishimura Y Nucleic Acids Res. 2017 Oct 24. doi: 10.1093/nar/gkx970. PMID:29069470[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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