Evidence map›Paper›PMID 33077952›Full record

ArticleNature structural & molecular biology2021

Dimers of DNA-PK create a stage for DNA double-strand break repair.

Amanda K Chaplin, Steven W Hardwick, Shikang Liang, Antonia Kefala Stavridi, Ales Hnizda, Lee R Cooper, Taiana Maia De Oliveira, Dimitri Y Chirgadze, Tom L Blundell

Abstract read
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In one paragraph

Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
6.5field-weighted citation impact, top 2% 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

70 citing papers in PubMed, 123 citations in OpenAlex.

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  19. Identification of 6-Anilino Imidazo[4,5-Journal of medicinal chemistry · 2024
    Article
  20. Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024
    Review

10 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Amanda K Chaplin *Department of Biochemistry, University of Cambridge, Cambridge, UK.
Steven W Hardwick *CryoEM Facility, Department of Biochemistry, University of Cambridge, Cambridge, UK.
Shikang LiangDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Antonia Kefala StavridiDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Ales HnizdaDepartment of Biochemistry, University of Cambridge, Cambridge, UK.
Lee R CooperCryoEM Facility, Department of Biochemistry, University of Cambridge, Cambridge, UK.
Taiana Maia De OliveiraAstraZeneca R&D, Discovery Sciences, Structure, Biophysics and FBLG, Cambridge, UK.
Dimitri Y ChirgadzeCryoEM Facility, Department of Biochemistry, University of Cambridge, Cambridge, UK.
Tom L BlundellDepartment of Biochemistry, University of Cambridge, Cambridge, UK. tlb20@cam.ac.uk.ORCID http://orcid.org/0000-0002-2708-8992
University of Cambridge · GBAstraZeneca (United Kingdom) · GB

Funding

Wellcome Trust 200814/Z/16/ZWellcome Trust O93167/Z/10/Z
6 · The paper itself

Abstract

DNA double-strand breaks are the most dangerous type of DNA damage and, if not repaired correctly, can lead to cancer. In humans, Ku70/80 recognizes DNA broken ends and recruits the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form DNA-dependent protein kinase holoenzyme (DNA-PK) in the process of non-homologous end joining (NHEJ). We present a 2.8-Å-resolution cryo-EM structure of DNA-PKcs, allowing precise amino acid sequence registration in regions uninterpreted in previous 4.3-Å X-ray maps. We also report a cryo-EM structure of DNA-PK at 3.5-Å resolution and reveal a dimer mediated by the Ku80 C terminus. Central to dimer formation is a domain swap of the conserved C-terminal helix of Ku80. Our results suggest a new mechanism for NHEJ utilizing a DNA-PK dimer to bring broken DNA ends together. Furthermore, drug inhibition of NHEJ in combination with chemo- and radiotherapy has proved successful, making these models central to structure-based drug targeting efforts.

Indexed as

DNA Breaks, Double-StrandedAmino Acid SequenceCryoelectron MicroscopyCrystallography, X-RayDimerizationDNADNA-Activated Protein KinaseDNA End-Joining RepairHumansKu AutoantigenMolecular ConformationDNADNA-Activated Protein KinaseKu AutoantigenPRKDC protein, humanXRCC5 protein, humanXrcc6 protein, human

Identifiers

PMID33077952
OpenAlexW3080185191

What OpenQuestion holds

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Read underepoch 390

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.