Evidence map›Paper›PMID 34417448›Full record

ArticleNature communications2021

Structural basis for proficient oxidized ribonucleotide insertion in double strand break repair.

Joonas A Jamsen, Akira Sassa, Lalith Perera, David D Shock, William A Beard, Samuel H Wilson

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

14 citing papers in PubMed, 16 citations in OpenAlex.

  1. Structural basis of transcription-coupled RNA damage by incorporation of oxidized ribonucleotides.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  4. Review
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  12. Polλ promotes microhomology-mediated end-joining.Nature structural & molecular biology · 2023
    Article
  13. Article
  14. Epidemiology of Δ8THC-Related Carcinogenesis in USA: A Panel Regression and Causal Inferential Study.International journal of environmental research and public health · 2022
    Article
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

6 authors at 2 institutions in 2 countries.

Joonas A JamsenGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. joonas.jamsen@nih.gov.ORCID 0000-0001-9505-1254
Akira SassaLaboratory of Chromatin Metabolism and Epigenetics, Graduate School of Science, Chiba University, Chiba, Japan.
Lalith PereraGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.ORCID 0000-0003-0823-1631
David D ShockGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
William A BeardGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Samuel H WilsonGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA. wilson5@niehs.nih.gov.ORCID 0000-0002-1702-5293
National Institutes of Health · USChiba University · JP

Funding

Nucleic Acid Enzymes--Pol Beta And Base Repair EnzymesZ01ES050158 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 1997 to 2008
$2.8M
MACROMOLECULAR MODELING AND CARCINOGENESISZ01ES043010 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DARDEN, THOMAS A · 1986 to 2008
$1.2M
Molecular Architecture of Oxidative Stress Induced Double Strand Break RepairR00ES029572 · NIEHS · UNIV OF ARKANSAS FOR MED SCIS · PI JOONAS JAMSEN · 2023 to 2026
$747k
STRUCTURE-ACTIVITY RELATIONSHIPS OF HIV-1 REVERSE TRANSCRIPTASEZ01ES050161 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 1997 to 2008
$241k
Intramural NIH HHS Z01 ES043010Intramural NIH HHS Z01 ES050158Intramural NIH HHS Z01 ES050161NIEHS NIH HHS R00 ES029572
6 · The paper itself

Abstract

Reactive oxygen species (ROS) oxidize cellular nucleotide pools and cause double strand breaks (DSBs). Non-homologous end-joining (NHEJ) attaches broken chromosomal ends together in mammalian cells. Ribonucleotide insertion by DNA polymerase (pol) μ prepares breaks for end-joining and this is required for successful NHEJ in vivo. We previously showed that pol μ lacks discrimination against oxidized dGTP (8-oxo-dGTP), that can lead to mutagenesis, cancer, aging and human disease. Here we reveal the structural basis for proficient oxidized ribonucleotide (8-oxo-rGTP) incorporation during DSB repair by pol μ. Time-lapse crystallography snapshots of structural intermediates during nucleotide insertion along with computational simulations reveal substrate, metal and side chain dynamics, that allow oxidized ribonucleotides to escape polymerase discrimination checkpoints. Abundant nucleotide pools, combined with inefficient sanitization and repair, implicate pol μ mediated oxidized ribonucleotide insertion as an emerging source of widespread persistent mutagenesis and genomic instability.

Indexed as

DNA Breaks, Double-StrandedDNA RepairAdenineCalciumCatalytic DomainCytosineDeoxyguanine NucleotidesDNA-Directed DNA PolymeraseHumansKineticsManganeseModels, MolecularOxidation-ReductionRibonucleotides8-oxodeoxyguanosine triphosphateAdenineCalciumCytosineDeoxyguanine NucleotidesDNA-Directed DNA PolymeraseDNA polymerase muManganeseRibonucleotides

Identifiers

PMID34417448
PMCPMC8379156
OpenAlexW3193903248

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.