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PXD025328-1

PXD025328 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructural basis of human transcription-DNA repair coupling
DescriptionTranscription-coupled DNA repair (TCR) efficiently removes bulky DNA lesions from transcribed parts of the genome and constitutes a major defence against DNA damage by UV irradiation. TCR begins when RNA polymerase II (Pol II) stalls at a DNA lesion and recruits the Cockayne syndrome protein CsB, the E3 ubiquitin ligase complex CRL4CsA, and the UV-stimulated scaffold protein A (UVSSA). Here we provide five high-resolution structures of Pol II transcription complexes with bound TCR factors and complementary biochemical data. Together with published work, our results converge on a model for the molecular mechanism of transcription-DNA repair coupling. In this model, Pol II stalling triggers the formation of an alternative transcription elongation complex that we call ECact. In ECact, CsB has replaced the elongation factor DSIF, binds the PAF1 complex, and repositions upstream DNA such that it contacts the elongation factor SPT6. The CsB translocase now pulls on the upstream DNA template, thereby pushing Pol II forward. If the lesion cannot be bypassed, Pol II gets stably stalled. CRL4CsA spans over the Pol II clamp to reach the Pol II jaw and direct ubiquitination of RPB1 residue lysine-1268. This triggers the recruitment of TFIIH to UVSSA, which is located at downstream DNA, and enables nucleotide excision repair. Finally, large-scale conformational changes in CRL4CsA enable ubiquitination of CsB and the release of TCR factors, thereby allowing Pol II to resume elongation and continue transcription over repaired DNA.
HostingRepositoryPRIDE
AnnounceDate2022-02-17
AnnouncementXMLSubmission_2022-02-17_00:53:44.251.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAleksandar Chernev
SpeciesList scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion; Q Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-12 19:25:54ID requested
12022-02-17 00:53:45announced
Publication List
Kokic G, Wagner FR, Chernev A, Urlaub H, Cramer P, Structural basis of human transcription-DNA repair coupling. Nature, 598(7880):368-372(2021) [pubmed]
Keyword List
submitter keyword: Protein-protein crosslinking, Ubiquitination analysis, Transcription-DNA repair
Contact List
Patrick Cramer
contact affiliationMax Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany
contact emailpatrick.cramer@mpibpc.mpg.de
lab head
Aleksandar Chernev
contact affiliationMPIbpc
contact emailaleksandar.chernev@mpibpc.mpg.de
dataset submitter
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Dataset FTP location
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