PreprintCited by 69DNA Repair MechanismsGenomics and Chromatin DynamicsChromatin Remodeling and Cancer

A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair

Open access
van den Heuvel, Diana, Spruijt, Cornelia G., González-Prieto, Román, Kragten, Angela, Paulsen, Michelle T., Zhou, Di, Wu, Haoyu, Apelt, Katja +9 more·2020·Nature Communications

Preprint — published as 10.1038/s41467-021-21520-w · Paper page

Abstract

The coordinated transcription of genes involves the regulated release of RNA polymerase II (RNAPII) from promoter-proximal sites into active elongation. DNA lesions in transcribed strands block elongation and induce a strong transcriptional arrest. The transcription-coupled repair (TCR) pathway efficiently removes transcription-blocking DNA lesions, but this is not sufficient to resume transcription. Through proteomics screens, we find that the TCR-specific CSB protein loads the evolutionary conserved PAF1 complex (PAF1C) onto RNAPII in promoter-proximal regions in response to DNA damage. PAF1C is dispensable for TCR-mediated repair, but is essential for recovery of RNA synthesis after UV irradiation, suggesting an uncoupling between DNA repair and transcription recovery. Moreover, we find that PAF1C promotes RNAPII pause release in promoter-proximal regions and subsequently acts as a processivity factor that stimulates transcription elongation throughout genes. Our findings expose the molecular basis for a non-canonical PAF1C-dependent pathway that restores transcription throughout the human genome after genotoxic stress.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2020.01.04.894808

Cites

76 of 76 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

2 of the 78 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
van den Heuvel, D., Spruijt, C. G., González-Prieto, R., Kragten, A., Paulsen, M. T., Zhou, D., Wu, H., Apelt, K., van der Weegen, Y., Yang, K., Dijk, M., Daxinger, L., Marteijn, J. A., Vertegaal, A. C. O., Ljungman, M., Vermeulen, M., & Luijsterburg, M. S.
Affiliations
  • Radboud University Nijmegen (NL)
  • Leiden University Medical Center (NL)
  • University of Michigan (US)
  • Oncode Institute (NL)
Corresponding author
Luijsterburg, Martijn S.
Venue
Nature Communications
Publisher
openRxiv
Published
2020-01-05
Volume
12
Issue
1
Pages
1342-1342
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3131547871
Cited by
69
References
78
Citations by year
2026: 6 · 2025: 16 · 2024: 12 · 2023: 12 · 2022: 10 · 2021: 11 · 2020: 2
FWCI
3.53
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (acceptedVersion, cc-by)
  • Leiden Repository (Leiden University) (submittedVersion, cc-by)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
Funders
  • Universiteit Leiden
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (ALW.016.161.320, VI.C.182.025, 016.161.320)
  • KWF Kankerbestrijding (11367)
  • Leids Universitair Medisch Centrum
  • Oncode Institute
  • National Institute of General Medical Sciences (T32GM070449)
  • FP7 Ideas: European Research Council (310913)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
CSB, Paf1 complex, RNA polymerase II, transcription elongation, transcription-coupled repair, DNA damage, UV irradiation, promoter-proximal pausing, processivity factor, genotoxic stress, transcriptional arrest
MeSH terms
Poly-ADP-Ribose Binding Proteins, Cell Nucleus, DNA, DNA Damage, DNA Repair, DNA Helicases, Humans, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Ultraviolet Rays, DNA Repair Enzymes, Protein Interaction Maps

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review