Evidence map›Paper›PMID 39578493›Full record

ArticleNature communications2024

Single-molecule imaging reveals the kinetics of non-homologous end-joining in living cells.

Mariia Mikhova, Noah J Goff, Tomáš Janovič, Joshua R Heyza, Katheryn Meek, Jens C Schmidt

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Mariia MikhovaDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Noah J GoffDepartment of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, MI, USA.ORCID 0000-0002-4925-4146
Tomáš JanovičInstitute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.ORCID 0000-0003-4471-5756
Joshua R HeyzaInstitute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.ORCID 0000-0003-0847-0501
Katheryn MeekDepartment of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, MI, USA.ORCID 0000-0002-0454-4414
Jens C SchmidtInstitute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA. schmi706@msu.edu.ORCID 0000-0001-9061-7853

Funding

Single-molecule Analysis of the DNA Damage Response in Living CellsDP2GM142307 · NIGMS · MICHIGAN STATE UNIVERSITY · PI SCHMIDT, JENS CHRISTOPHER · 2020 to 2020
$2.1M
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
Defining the mechanism of Shieldin complex in DNA end joiningF32GM139292 · NIGMS · MICHIGAN STATE UNIVERSITY · PI HEYZA, JOSHUA · 2020 to 2022
$201k
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) R01AI147634NIAID NIH HHS R01 AI147634NIGMS NIH HHS DP2 GM142307NIGMS NIH HHS F32 GM139292U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) DP2GM142307U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) F32GM139292
6 · The paper itself

Abstract

Non-homologous end joining (NHEJ) is the predominant pathway that repairs DNA double-stranded breaks (DSBs) in vertebrates. However, due to challenges in detecting DSBs in living cells, the repair capacity of the NHEJ pathway is unknown. The DNA termini of many DSBs must be processed to allow ligation while minimizing genetic changes that result from break repair. Emerging models propose that DNA termini are first synapsed ~115 Å apart in one of several long-range synaptic complexes before transitioning into a short-range synaptic complex that juxtaposes DNA ends to facilitate ligation. The transition from long-range to short-range synaptic complexes involves both conformational and compositional changes of the NHEJ factors bound to the DNA break. Importantly, it is unclear how NHEJ proceeds in vivo because of the challenges involved in analyzing recruitment of NHEJ factors to DSBs over time in living cells. Here, we develop an approach to study the temporal and compositional dynamics of NHEJ complexes using live cell single-molecule imaging. Our results provide direct evidence for stepwise maturation of the NHEJ complex, pinpoint key regulatory steps in NHEJ progression, and allowed us to estimate the overall repair capacity of the NHEJ pathway in living cells.

Indexed as

DNA Breaks, Double-StrandedDNA End-Joining RepairSingle Molecule ImagingAnimalsDNADNA-Binding ProteinsDNA Repair EnzymesHumansKineticsDNADNA-Binding ProteinsDNA Repair Enzymes

Identifiers

PMID39578493
PMCPMC11584804

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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.