Evidence map›Paper›PMID 36323657›Full record

ArticleNature communications2022

Structural dynamics of DNA strand break sensing by PARP-1 at a single-molecule level.

Anna Sefer, Eleni Kallis, Tobias Eilert, Carlheinz Röcker, Olga Kolesnikova, David Neuhaus, Sebastian Eustermann, Jens Michaelis

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Prospects for PARG inhibitors in cancer therapy.Journal of molecular cell biology · 2025
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Long non-coding RNANon-coding RNA research · 2024
    Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 2 countries.

Anna Sefer *Institute of Biophysics, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
Eleni Kallis *Institute of Biophysics, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
Tobias EilertInstitute of Biophysics, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
Carlheinz RöckerInstitute of Biophysics, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
Olga KolesnikovaEuropean Molecular Biology Laboratory (EMBL), Heidelberg Meyerhofstraße 1, 69117, Heidelberg, Germany.
David NeuhausMRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge, CB2 0QH, UK.ORCID 0000-0002-8561-7485
Sebastian EustermannEuropean Molecular Biology Laboratory (EMBL), Heidelberg Meyerhofstraße 1, 69117, Heidelberg, Germany. jens.michaelis@uni-ulm.de.ORCID 0000-0002-4439-7770
Jens MichaelisInstitute of Biophysics, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany. sebastian.eustermann@embl.de.ORCID 0000-0002-2739-4172
Universität Ulm · DEBoehringer Ingelheim (Germany) · DEEuropean Molecular Biology Laboratory · DEEuropean Molecular Biology Laboratory · DEMRC Laboratory of Molecular Biology · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Single-stranded breaks (SSBs) are the most frequent DNA lesions threatening genomic integrity. A highly kinked DNA structure in complex with human PARP-1 domains led to the proposal that SSB sensing in Eukaryotes relies on dynamics of both the broken DNA double helix and PARP-1's multi-domain organization. Here, we directly probe this process at the single-molecule level. Quantitative smFRET and structural ensemble calculations reveal how PARP-1's N-terminal zinc fingers convert DNA SSBs from a largely unperturbed conformation, via an intermediate state into the highly kinked DNA conformation. Our data suggest an induced fit mechanism via a multi-domain assembly cascade that drives SSB sensing and stimulates an interplay with the scaffold protein XRCC1 orchestrating subsequent DNA repair events. Interestingly, a clinically used PARP-1 inhibitor Niraparib shifts the equilibrium towards the unkinked DNA conformation, whereas the inhibitor EB47 stabilizes the kinked state.

Indexed as

DNA Breaks, Single-StrandedPoly(ADP-ribose) Polymerase InhibitorsDNADNA DamageDNA RepairHumansX-ray Repair Cross Complementing Protein 1DNAPoly(ADP-ribose) Polymerase InhibitorsX-ray Repair Cross Complementing Protein 1XRCC1 protein, human

Identifiers

PMID36323657
PMCPMC9630430
OpenAlexW4308147072

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.