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-Structure paper
タイトル | Elf1 promotes Rad26's interaction with lesion-arrested Pol II for transcription-coupled repair. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 121, Issue 3, Page e2314245121, Year 2024 |
掲載日 | 2024年1月16日 |
著者 | Reta D Sarsam / Jun Xu / Indrajit Lahiri / Wenzhi Gong / Qingrong Li / Juntaek Oh / Zhen Zhou / Peini Hou / Jenny Chong / Nan Hao / Shisheng Li / Dong Wang / Andres E Leschziner / |
PubMed 要旨 | Transcription-coupled nucleotide excision repair (TC-NER) is a highly conserved DNA repair pathway that removes bulky lesions in the transcribed genome. Cockayne syndrome B protein (CSB), or its ...Transcription-coupled nucleotide excision repair (TC-NER) is a highly conserved DNA repair pathway that removes bulky lesions in the transcribed genome. Cockayne syndrome B protein (CSB), or its yeast ortholog Rad26, has been known for decades to play important roles in the lesion-recognition steps of TC-NER. Another conserved protein ELOF1, or its yeast ortholog Elf1, was recently identified as a core transcription-coupled repair factor. How Rad26 distinguishes between RNA polymerase II (Pol II) stalled at a DNA lesion or other obstacles and what role Elf1 plays in this process remains unknown. Here, we present cryo-EM structures of Pol II-Rad26 complexes stalled at different obstacles that show that Rad26 uses a common mechanism to recognize a stalled Pol II, with additional interactions when Pol II is arrested at a lesion. A cryo-EM structure of lesion-arrested Pol II-Rad26 bound to Elf1 revealed that Elf1 induces further interactions between Rad26 and a lesion-arrested Pol II. Biochemical and genetic data support the importance of the interplay between Elf1 and Rad26 in TC-NER initiation. Together, our results provide important mechanistic insights into how two conserved transcription-coupled repair factors, Rad26/CSB and Elf1/ELOF1, work together at the initial lesion recognition steps of transcription-coupled repair. |
リンク | Proc Natl Acad Sci U S A / PubMed:38194460 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.1 - 4.6 Å |
構造データ | EMDB-41623, PDB-8tug: EMDB-41647, PDB-8tvp: EMDB-41648, PDB-8tvq: EMDB-41650, PDB-8tvs: EMDB-41652, PDB-8tvv: EMDB-41653, PDB-8tvw: EMDB-41654, PDB-8tvx: EMDB-41655, PDB-8tvy: |
化合物 | ChemComp-ZN: ChemComp-MG: |
由来 |
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キーワード | TRANSCRIPTION/DNA/RNA / RNA Polymerase II / Rad26 / CPD lesion / Transcription-coupled DNA repair / TRANSCRIPTION / TRANSCRIPTION-DNA-RNA complex / Backtracked Polymerase |