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  Structural basis of human transcription–DNA repair coupling

Kokic, G., Wagner, F. R., Chernev, A., Urlaub, H., & Cramer, P. (2021). Structural basis of human transcription–DNA repair coupling. Nature, 598(7880), 368-372. doi:10.1038/s41586-021-03906-4.

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 Creators:
Kokic, G.1, Author              
Wagner, F. R.1, Author              
Chernev, A.2, Author              
Urlaub, H.3, Author              
Cramer, P.1, Author              
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              
2Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society, ou_578613              
3Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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Free keywords: Cryoelectron microscopy; DNA damage and repair; Transcription
 Abstract: Transcription-coupled DNA repair removes bulky DNA lesions from the genome1,2 and protects cells against ultraviolet (UV) irradiation3. 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, CRL4CSA and UV-stimulated scaffold protein A (UVSSA)3. 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 published3,4 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, ECTCR, uses the CSA-stimulated translocase activity of CSB to pull on upstream DNA and push Pol II forward. If the lesion cannot be bypassed, CRL4CSA spans over the Pol II clamp and ubiquitylates the RPB1 residue K1268, enabling recruitment of TFIIH to UVSSA and DNA repair. Conformational changes in CRL4CSA lead to ubiquitylation of CSB and to release of transcription-coupled DNA repair factors before transcription may continue over repaired DNA.

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Language(s): eng - English
 Dates: 2021-09-152021-10-14
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41586-021-03906-4
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Title: Nature
Source Genre: Journal
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Pages: - Volume / Issue: 598 (7880) Sequence Number: - Start / End Page: 368 - 372 Identifier: -