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Structure of TFIIH/Rad4-Rad23-Rad33/DNA in DNA openingStructure of TFIIH/Rad4-Rad23-Rad33/DNA in DNA opening
Structural highlights
FunctionRAD3_YEAST ATP-dependent DNA helicase involved in excision repair of DNA damaged with UV light, bulky adducts, or cross-linking agents. Necessary for excision of pyrimidine dimers. Also unwinds DNA/RNA duplexes. Plays an essential role in the cell viability. Involved in the maintenance of the fidelity of DNA replication. Acts as component of the general transcription and DNA repair factor IIH (TFIIH) core, which is essential for both basal and activated transcription, and is involved in nucleotide excision repair (NER) of damaged DNA. TFIIH has CTD kinase and DNA-dependent ATPase activity, and is essential for polymerase II transcription in vitro.[1] [2] Publication Abstract from PubMedThe versatile nucleotide excision repair (NER) pathway initiates as the XPC-RAD23B-CETN2 complex first recognizes DNA lesions from the genomic DNA and recruits the general transcription factor complex, TFIIH, for subsequent lesion verification. Here, we present a cryo-EM structure of an NER initiation complex containing Rad4-Rad23-Rad33 (yeast homologue of XPC-RAD23B-CETN2) and 7-subunit coreTFIIH assembled on a carcinogen-DNA adduct lesion at 3.9-9.2 A resolution. A ~30-bp DNA duplex could be mapped as it straddles between Rad4 and the Ssl2 (XPB) subunit of TFIIH on the 3' and 5' side of the lesion, respectively. The simultaneous binding with Rad4 and TFIIH was permitted by an unwinding of DNA at the lesion. Translocation coupled with torque generation by Ssl2 and Rad4 would extend the DNA unwinding at the lesion and deliver the damaged strand to Rad3 (XPD) in an open form suitable for subsequent lesion scanning and verification. Cryo-EM structure of TFIIH/Rad4-Rad23-Rad33 in damaged DNA opening in nucleotide excision repair.,van Eeuwen T, Shim Y, Kim HJ, Zhao T, Basu S, Garcia BA, Kaplan CD, Min JH, Murakami K Nat Commun. 2021 Jun 7;12(1):3338. doi: 10.1038/s41467-021-23684-x. PMID:34099686[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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