Evidence map›Paper›PMID 25539919›Full record

ArticleNucleic acids research2015

Tumor-associated mutations in a conserved structural motif alter physical and biochemical properties of human RAD51 recombinase.

Jianhong Chen, Milagros D Morrical, Katherine A Donigan, Joanne B Weidhaas, Joann B Sweasy, April M Averill, Jennifer A Tomczak, Scott W Morrical

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. 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
1.1field-weighted citation impact, top 22% 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, 29 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

8 authors at 3 institutions in 1 country.

Jianhong ChenDepartment of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Milagros D MorricalDepartment of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Katherine A DoniganDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Joanne B WeidhaasDepartment of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Joann B SweasyDepartment of Microbiology and Molecular Genetics, University of Vermont College of Medicine, Burlington, VT 05405, USA Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
April M AverillDepartment of Microbiology and Molecular Genetics, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Jennifer A TomczakDepartment of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Scott W MorricalDepartment of Biochemistry, University of Vermont College of Medicine, Burlington, VT 05405, USA Department of Microbiology and Molecular Genetics, University of Vermont College of Medicine, Burlington, VT 05405, USA smorrica@uvm.edu.
University of Vermont · USYale University · USUniversity of California, Los Angeles · US

Funding

SUBSTRATE SPECIFICITY OF THE BER OXIDATIVE DNA GLYCOSYLASESP01CA098993 · NCI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI DOUBLIE, SYLVIE · 2004 to 2021
$25.9M
MicroRNAs to Understand Cause and Outcome in Breast CancerR01CA157749 · NCI · YALE UNIVERSITY · PI SLACK, FRANK J., WEIDHAAS, JOANNE B · 2012 to 2016
$1.7M
NCI NIH HHS CA098993NCI NIH HHS P01 CA098993NCI NIH HHS R01 CA157749NIGMS NIH HHS GM007499
6 · The paper itself

Abstract

Human RAD51 protein catalyzes DNA pairing and strand exchange reactions that are central to homologous recombination and homology-directed DNA repair. Successful recombination/repair requires the formation of a presynaptic filament of RAD51 on ssDNA. Mutations in BRCA2 and other proteins that control RAD51 activity are associated with human cancer. Here we describe a set of mutations associated with human breast tumors that occur in a common structural motif of RAD51. Tumor-associated D149N, R150Q and G151D mutations map to a Schellman loop motif located on the surface of the RecA homology domain of RAD51. All three variants are proficient in DNA strand exchange, but G151D is slightly more sensitive to salt than wild-type (WT). Both G151D and R150Q exhibit markedly lower catalytic efficiency for adenosine triphosphate hydrolysis compared to WT. All three mutations alter the physical properties of RAD51 nucleoprotein filaments, with G151D showing the most dramatic changes. G151D forms mixed nucleoprotein filaments with WT RAD51 that have intermediate properties compared to unmixed filaments. These findings raise the possibility that mutations in RAD51 itself may contribute to genome instability in tumor cells, either directly through changes in recombinase properties, or indirectly through changes in interactions with regulatory proteins.

Indexed as

MutationAdenosine TriphosphateAmino Acid MotifsDNAHumansModels, MolecularNeoplasmsProtein FoldingRad51 RecombinaseAdenosine TriphosphateDNARad51 Recombinase

Identifiers

PMID25539919
PMCPMC4333388
OpenAlexW2165394526

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.