Evidence map›Paper›PMID 27513445›Full record

ArticlePLoS genetics2016

The Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype.

Carolyn G Marsden, Ryan B Jensen, Jennifer Zagelbaum, Eli Rothenberg, Scott W Morrical, Susan S Wallace, Joann B Sweasy

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

18 citing papers in PubMed, 30 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

Carolyn G MarsdenDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
Ryan B JensenDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Jennifer ZagelbaumDepartment of Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, New York, United States of America.
Eli RothenbergDepartment of Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, New York, United States of America.
Scott W MorricalDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
Susan S WallaceDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
Joann B SweasyDepartment of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America.
University of Vermont · USNew York University · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
SUBSTRATE SPECIFICITY OF THE BER OXIDATIVE DNA GLYCOSYLASESP01CA098993 · NCI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI DOUBLIE, SYLVIE · 2004 to 2021
$25.9M
PH REGULATION OF CONNEXIN43--INTERMEDIARY STEPSR01GM057691 · NIGMS · UPSTATE MEDICAL UNIVERSITY · PI DELMAR, MARIO · 1999 to 2016
$5.6M
Single-Molecule Studies of Non-Homologous DNA End JoiningR01GM108119 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ROTHENBERG, ELI · 2015 to 2019
$1.7M
INVERTED LASER-SCANNING CONFOCAL MICROSCOPE: LUNG RESEARCHS10RR019246 · NCRR · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI TAATJES, DOUGLAS J. · 2004 to 2004
$473k
Single-molecule studies of BRCA1-BACH1 mechanism in genomic integrityR21CA187612 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ROTHENBERG, ELI · 2015 to 2016
$451k
NCI NIH HHS P01 CA098993NCI NIH HHS R21 CA187612NCRR NIH HHS S10 RR019246NIGMS NIH HHS R01 GM057691NIGMS NIH HHS R01 GM108119
6 · The paper itself

Abstract

The RAD51 protein plays a key role in the homology-directed repair of DNA double-strand breaks and is important for maintaining genome stability. Here we report on a novel human RAD51 variant found in an aggressive and therapy-refractive breast carcinoma. Expression of the RAD51 G151D variant in human breast epithelial cells increases the levels of homology-directed repair. Expression of RAD51 G151D in cells also promotes high levels of chromosomal aberrations and sister chromatid exchanges. In vitro, the purified RAD51 G151D protein directly and significantly enhances DNA strand exchange activity in the presence of RPA. In concordance with this result, co-incubation of G151D with BRCA2 resulted in a much higher level of strand-exchange activity compared to WT RAD51. Strikingly, the RAD51 G151D variant confers resistance to multiple DNA damaging agents, including ionizing radiation, mitomycin C, and doxorubicin. Our findings demonstrate that the RAD51 G151D somatic variant has a novel hyper-recombination phenotype and suggest that this property of the protein is important for the repair of DNA damage, leading to drug resistance.

Indexed as

BRCA2 ProteinBreast NeoplasmsChromosome AberrationsDNA Breaks, Double-StrandedDNA DamageDNA RepairDoxorubicinFemaleGene Expression Regulation, NeoplasticGenomic InstabilityHumansMCF-7 CellsMitomycinMutationRad51 RecombinaseRadiation, IonizingBRCA2 ProteinBRCA2 protein, humanDoxorubicinMitomycinRad51 Recombinase

Identifiers

PMID27513445
PMCPMC4981402
OpenAlexW2513670757

What OpenQuestion holds

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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.