Evidence map›Paper›PMID 33658195›Full record

ArticleScience advances2021

Exonuclease VII repairs quinolone-induced damage by resolving DNA gyrase cleavage complexes.

Shar-Yin N Huang, Stephanie A Michaels, Brianna B Mitchell, Nadim Majdalani, Arnaud Vanden Broeck, Andres Canela, Yuk-Ching Tse-Dinh, Valerie Lamour, Yves Pommier

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. DNA repair is essential forJournal of bacteriology · 2025
    Article
  4. Article
  5. DNA repair is essential forbioRxiv : the preprint server for biology · 2025
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  6. Review
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  12. Structure ofProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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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 4 institutions in 3 countries.

Shar-Yin N HuangLaboratory of Molecular Pharmacology, Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. shar-yin.huang@nih.gov pommier@nih.gov.ORCID 0000-0002-4772-428X
Stephanie A MichaelsLaboratory of Molecular Pharmacology, Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Brianna B MitchellLaboratory of Molecular Pharmacology, Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Nadim MajdalaniLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.ORCID 0000-0002-9314-5203
Arnaud Vanden BroeckIntegrated Structural Biology Department, IGBMC, UMR7104 CNRS, U1258 Inserm, University of Strasbourg, Illkirch 67404, France.ORCID 0000-0003-0930-4249
Andres CanelaThe Hakubi Center for Advanced Research, Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.ORCID 0000-0002-3621-6706
Yuk-Ching Tse-DinhDepartment of Chemistry and Biochemistry, Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA.ORCID 0000-0002-5616-5176
Valerie LamourIntegrated Structural Biology Department, IGBMC, UMR7104 CNRS, U1258 Inserm, University of Strasbourg, Illkirch 67404, France.ORCID 0000-0001-7793-4029
Yves PommierLaboratory of Molecular Pharmacology, Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. shar-yin.huang@nih.gov pommier@nih.gov.ORCID 0000-0002-3108-0758
National Cancer Institute · USCentre National de la Recherche Scientifique · FRFlorida International University · USKyoto University · JP

Funding

DNA Repair, Cell Cycle Checkpoints and Apoptosis as Targets for Anticancer DrugsZIABC006150 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 2009 to 2025
$23.0M
PROTEIN-ASSOCIATED DNA BREAKS AS INDICATOR OF TOPOISOMERASE INHIBITIONZ01BC006150 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 1996 to 2008
$1.5M
Intramural NIH HHS Z01 BC006150
6 · The paper itself

Abstract

The widely used quinolone antibiotics act by trapping prokaryotic type IIA topoisomerases, resulting in irreversible topoisomerase cleavage complexes (TOPcc). Whereas the excision repair pathways of TOPcc in eukaryotes have been extensively studied, it is not known whether equivalent repair pathways for prokaryotic TOPcc exist. By combining genetic, biochemical, and molecular biology approaches, we demonstrate that exonuclease VII (ExoVII) excises quinolone-induced trapped DNA gyrase, an essential prokaryotic type IIA topoisomerase. We show that ExoVII repairs trapped type IIA TOPcc and that ExoVII displays tyrosyl nuclease activity for the tyrosyl-DNA linkage on the 5'-DNA overhangs corresponding to trapped type IIA TOPcc. ExoVII-deficient bacteria fail to remove trapped DNA gyrase, consistent with their hypersensitivity to quinolones. We also identify an ExoVII inhibitor that synergizes with the antimicrobial activity of quinolones, including in quinolone-resistant bacterial strains, further demonstrating the functional importance of ExoVII for the repair of type IIA TOPcc.

Indexed as

DNA GyraseQuinolonesBacteriaDNAExonucleasesDNADNA GyraseExonucleasesQuinolones

Identifiers

PMID33658195
PMCPMC7929499
OpenAlexW3133633469

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.