Evidence map›Paper›PMID 34718766›Full record

ArticleNucleic acids research2021

MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage.

Teressa Paulsen, Pumoli Malapati, Yoshiyuki Shibata, Briana Wilson, Rebeka Eki, Mouadh Benamar, Tarek Abbas, Anindya Dutta

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 3% 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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
  2. Review
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  4. Article
  5. Functional role of small extrachromosomal circular DNA in colorectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  7. BRCA1-A and LIG4 complexes mediate ecDNA biogenesis and cancer drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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

8 authors at 3 institutions in 2 countries.

Teressa PaulsenDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Pumoli MalapatiDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Yoshiyuki ShibataDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Briana WilsonDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Rebeka EkiDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.ORCID 0000-0002-7007-4246
Mouadh BenamarDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Tarek AbbasDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.ORCID 0000-0003-1398-6545
Anindya DuttaDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.ORCID 0000-0002-3559-2574
University of Virginia · USUniversity of Alabama at Birmingham · USUniversity of Oxford · GB

Funding

Cancer Research Training Program: From Molecular Mechanisms to Therapeutic StrategiesT32CA009109 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Andrew Carl Dudley, Melanie R Rutkowski · 1985 to 2026
$13.9M
The role of MCM8-9 in genomic instability of cancersR01CA060499 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Anindya Dutta · 1994 to 2026
$8.6M
Regulation of re-replication in mammalian cellsR01GM135376 · NIGMS · UNIVERSITY OF VIRGINIA · PI ABBAS, TAREK A. · 2020 to 2024
$1.8M
Stability of a novel family of short noncoding RNAs, tRFs: Effect on oncogenesisF30CA254134 · NCI · UNIVERSITY OF VIRGINIA · PI WILSON, BRIANA · 2020 to 2022
$120k
NCI NIH HHS F30 CA254134NCI NIH HHS R01 CA060499NCI NIH HHS T32 CA009109NIGMS NIH HHS R01 GM135376
6 · The paper itself

Abstract

Extrachromosomal circular DNA (eccDNA) are present within all eukaryotic organisms and actively contribute to gene expression changes. MicroDNA (200-1000bp) are the most abundant type of eccDNA and can amplify tRNA, microRNA, and novel si-like RNA sequences. Due to the heterogeneity of microDNA and the limited technology to directly quantify circular DNA molecules, the specific DNA repair pathways that contribute to microDNA formation have not been fully elucidated. Using a sensitive and quantitative assay that quantifies eight known abundant microDNA, we report that microDNA levels are dependent on resection after double-strand DNA break (DSB) and repair by Microhomology Mediated End Joining (MMEJ). Further, repair of DSB without resection by canonical Non-Homologous End Joining (c-NHEJ) diminishes microDNA formation. MicroDNA levels are induced locally even by a single site-directed DSB, suggesting that excision of genomic DNA by two closely spaced DSB is not necessary for microDNA formation. Consistent with all this, microDNA levels accumulate as cells undergo replication in S-phase, when DNA breaks and repair are elevated, and microDNA levels are decreased if DNA synthesis is prevented. Thus, formation of microDNA occurs during the repair of endogenous or induced DNA breaks by resection-based DNA repair pathways.

Indexed as

DNA DamageDNA End-Joining RepairDNA, CircularDNA ReplicationHEK293 CellsHeLa CellsHumansDNA, Circular

Identifiers

PMID34718766
PMCPMC8599734
OpenAlexW3210471498

What OpenQuestion holds

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LicenceCC BY
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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.