Evidence map›Paper›PMID 34352203›Full record

ArticleMolecular cell2021

Cryo-EM of NHEJ supercomplexes provides insights into DNA repair.

Amanda K Chaplin, Steven W Hardwick, Antonia Kefala Stavridi, Christopher J Buehl, Noah J Goff, Virginie Ropars, Shikang Liang, Taiana Maia De Oliveira, Dimitri Y Chirgadze, Katheryn Meek and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
6.3field-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

62 citing papers in PubMed, 100 citations in OpenAlex.

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2 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

12 authors at 4 institutions in 3 countries.

Amanda K ChaplinDepartment of Biochemistry, University of Cambridge, Sanger Building, Tennis Court Road, Cambridge CB2 1GA, UK. Electronic address: ac821@cam.ac.uk.
Steven W HardwickCryoEM Facility, Department of Biochemistry, University of Cambridge, Sanger Building, Tennis Court Road, Cambridge CB2 1GA, UK.
Antonia Kefala StavridiDepartment of Biochemistry, University of Cambridge, Sanger Building, Tennis Court Road, Cambridge CB2 1GA, UK.
Christopher J BuehlCollege of Veterinary Medicine, Department of Microbiology & Molecular Genetics, Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Noah J GoffCollege of Veterinary Medicine, Department of Microbiology & Molecular Genetics, Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Virginie RoparsInstitute for Integrative Biology of the Cell (I2BC), Institute Joliot, CEA, CNRS, Université Paris-Saclay, 91198, Gif-sur-Yvette Cedex, France.
Shikang LiangDepartment of Biochemistry, University of Cambridge, Sanger Building, Tennis Court Road, Cambridge CB2 1GA, UK.
Taiana Maia De OliveiraAstraZeneca R&D, Discovery Sciences, Mechanistic and Structural Biology, Cambridge, UK.
Dimitri Y ChirgadzeCryoEM Facility, Department of Biochemistry, University of Cambridge, Sanger Building, Tennis Court Road, Cambridge CB2 1GA, UK.
Katheryn MeekCollege of Veterinary Medicine, Department of Microbiology & Molecular Genetics, Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Jean-Baptiste CharbonnierInstitute for Integrative Biology of the Cell (I2BC), Institute Joliot, CEA, CNRS, Université Paris-Saclay, 91198, Gif-sur-Yvette Cedex, France.
Tom L BlundellDepartment of Biochemistry, University of Cambridge, Sanger Building, Tennis Court Road, Cambridge CB2 1GA, UK. Electronic address: tlb20@cam.ac.uk.
University of Cambridge · GBMichigan State University · USUniversité Paris-Saclay · FRAstraZeneca (United Kingdom) · GB

Funding

Defining the mechanistic basis of ATM’s impact on VDJ recombinationR01AI147634 · NIAID · MICHIGAN STATE UNIVERSITY · PI MEEK, KATHERYN D, YU, KEFEI · 2019 to 2024
$1.9M
Does overexpression of DNA polymerase theta sensitize cancers to G-quadruplex binding drugs?R21CA240875 · NCI · MICHIGAN STATE UNIVERSITY · PI MEEK, KATHERYN D · 2019 to 2020
$371k
NCI NIH HHS R21 CA240875NIAID NIH HHS R01 AI147634Wellcome Trust 200814/Z/16/ZWellcome Trust O93167/Z/10/Z
6 · The paper itself

Abstract

Non-homologous end joining (NHEJ) is one of two critical mechanisms utilized in humans to repair DNA double-strand breaks (DSBs). Unrepaired or incorrect repair of DSBs can lead to apoptosis or cancer. NHEJ involves several proteins, including the Ku70/80 heterodimer, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), X-ray cross-complementing protein 4 (XRCC4), XRCC4-like factor (XLF), and ligase IV. These core proteins bind DSBs and ligate the damaged DNA ends. However, details of the structural assembly of these proteins remain unclear. Here, we present cryo-EM structures of NHEJ supercomplexes that are composed of these core proteins and DNA, revealing the detailed structural architecture of this assembly. We describe monomeric and dimeric forms of this supercomplex and also propose the existence of alternate dimeric forms of long-range synaptic complexes. Finally, we show that mutational disruption of several structural features within these NHEJ complexes negatively affects DNA repair.

Indexed as

ApoptosisCryoelectron MicroscopyDNA-Activated Protein KinaseDNA-Binding ProteinsDNA Breaks, Double-StrandedDNA DamageDNA End-Joining RepairDNA Ligase ATPDNA RepairDNA Repair EnzymesHumansKu AutoantigenMultiprotein ComplexesPhosphorylationDNA-Activated Protein KinaseDNA-Binding ProteinsDNA Ligase ATPDNA Repair EnzymesKu AutoantigenMultiprotein ComplexesNHEJ1 protein, humanPRKDC protein, humanXRCC4 protein, humanXRCC5 protein, humanXrcc6 protein, humancryo-EMDNA-PKDNA repairlong-range synaptic complexesNHEJnon-homologous end joining

Identifiers

PMID34352203
PMCPMC9006396
OpenAlexW3187829407

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.