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-Structure paper
タイトル | Structural basis of human transcription-DNA repair coupling. |
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ジャーナル・号・ページ | Nature, Vol. 598, Issue 7880, Page 368-372, Year 2021 |
掲載日 | 2021年9月15日 |
著者 | Goran Kokic / Felix R Wagner / Aleksandar Chernev / Henning Urlaub / Patrick Cramer / |
PubMed 要旨 | Transcription-coupled DNA repair removes bulky DNA lesions from the genome and protects cells against ultraviolet (UV) irradiation. Transcription-coupled DNA repair begins when RNA polymerase II ...Transcription-coupled DNA repair removes bulky DNA lesions from the genome and protects cells against ultraviolet (UV) irradiation. Transcription-coupled DNA repair begins when RNA polymerase II (Pol II) stalls at a DNA lesion and recruits the Cockayne syndrome protein CSB, the E3 ubiquitin ligase, CRL4 and UV-stimulated scaffold protein A (UVSSA). Here we provide five high-resolution structures of Pol II transcription complexes containing human transcription-coupled DNA repair factors and the elongation factors PAF1 complex (PAF) and SPT6. Together with biochemical and published data, the structures provide a model for transcription-repair coupling. Stalling of Pol II at a DNA lesion triggers replacement of the elongation factor DSIF by CSB, which binds to PAF and moves upstream DNA to SPT6. The resulting elongation complex, EC, uses the CSA-stimulated translocase activity of CSB to pull on upstream DNA and push Pol II forward. If the lesion cannot be bypassed, CRL4 spans over the Pol II clamp and ubiquitylates the RPB1 residue K1268, enabling recruitment of TFIIH to UVSSA and DNA repair. Conformational changes in CRL4 lead to ubiquitylation of CSB and to release of transcription-coupled DNA repair factors before transcription may continue over repaired DNA. |
リンク | Nature / PubMed:34526721 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.7 - 3.0 Å |
構造データ | EMDB-13004, PDB-7oo3: EMDB-13009, PDB-7oob: EMDB-13010, PDB-7oop: EMDB-13015, PDB-7opc: EMDB-13016, PDB-7opd: |
化合物 | ChemComp-ZN: ChemComp-MG: ChemComp-ADP: ChemComp-BEF: |
由来 |
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キーワード | TRANSCRIPTION / DNA repair / TCR / ubiquitin |