Evidence map›Paper›PMID 26145171›Full record

ArticleMolecular cell2015

Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry.

Weixing Zhao, Sivaraja Vaithiyalingam, Joseph San Filippo, David G Maranon, Judit Jimenez-Sainz, Gerald V Fontenay, Youngho Kwon, Stanley G Leung, Lucy Lu, Ryan B Jensen and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed
6.5field-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

118 citing papers in PubMed, 177 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
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  9. Phosphoregulation of RAD51AP1 function in homology-directed repair.bioRxiv : the preprint server for biology · 2025
    Article
  10. Article
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  12. Review
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  18. Article
  19. Structure of RADX and mechanism for regulation of RAD51 nucleofilaments.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. Article

58 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 1 country.

Weixing ZhaoDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
Sivaraja VaithiyalingamDepartments of Biochemistry and Chemistry, and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.
Joseph San FilippoDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
David G MaranonDepartment of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Judit Jimenez-SainzDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Gerald V FontenayLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Youngho KwonDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
Stanley G LeungLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Lucy LuDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
Ryan B JensenDepartment of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Walter J ChazinDepartments of Biochemistry and Chemistry, and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: walter.chazin@vanderbilt.edu.
Claudia WieseDepartment of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Patrick SungDepartment of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: patrick.sung@yale.edu.
Yale University · USColorado State University · USLawrence Berkeley National Laboratory · USVanderbilt University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Structural Biology Facility CoreP30ES000267 · NIEHS · VANDERBILT UNIVERSITY · PI GUENGERICH, F PETER · 1985 to 2014
$20.3M
YEAST DNA REPAIR GENES AND PROTEINS OF THE RAD52 GROUPR01ES007061 · NIEHS · YALE UNIVERSITY · PI Patrick Sung · 1995 to 2026
$9.4M
MOLECULAR BIOPHYSICS TRAINING PROGRAM AT VANDERBILTT32GM008320 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 1989 to 2023
$7.9M
Mechanistic Dissection of the Fanconi Anemia Pathway of DNA Damage Response and RR01CA168635 · NCI · YALE UNIVERSITY · PI Gary M Kupfer, Patrick Sung · 2013 to 2026
$5.8M
Structural Basis for RPA Functions in DNA ProcessingR01GM065484 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 2003 to 2015
$3.9M
Molecular Basis of BRCA2-mediated DNA Repair and Cancer AvoidanceR01ES015252 · NIEHS · YALE UNIVERSITY · PI SUNG, PATRICK · 2007 to 2016
$3.8M
NUCKS, a novel double-strand break repair gene, implicated in cancer biologyR01ES021454 · NIEHS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI WIESE, CLAUDIA · 2012 to 2016
$1.9M
High-Performance Computer Cluster for Biomedical ResearchS10OD023680 · OD · VANDERBILT UNIVERSITY · PI MEILER, JENS · 2017 to 2017
$587k
Console upgrades for biological NMR spectrometersS10RR025677 · NCRR · VANDERBILT UNIVERSITY · PI SANDERS, CHARLES R · 2009 to 2009
$460k
Define the role of NUCKS1 in homologous recombination DNA repair and cancer biologyR56ES021454 · NIEHS · COLORADO STATE UNIVERSITY · PI WIESE, CLAUDIA · 2019 to 2019
$225k
NCI NIH HHS CA168635NCI NIH HHS CA92584NCI NIH HHS P01 CA092584NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA168635NCRR NIH HHS S10 RR025677NIEHS NIH HHS ES007061NIEHS NIH HHS ES015252NIEHS NIH HHS ES021454NIEHS NIH HHS P30 ES000267NIEHS NIH HHS P30 ES00267NIEHS NIH HHS R01 ES007061NIEHS NIH HHS R01 ES015252NIEHS NIH HHS R01 ES021454NIEHS NIH HHS R56 ES021454NIGMS NIH HHS GM65484NIGMS NIH HHS R01 GM065484NIGMS NIH HHS T32 GM008320NIH HHS S10 OD023680
6 · The paper itself

Abstract

The tumor suppressor BRCA2 is thought to facilitate the handoff of ssDNA from replication protein A (RPA) to the RAD51 recombinase during DNA break and replication fork repair by homologous recombination. However, we find that RPA-RAD51 exchange requires the BRCA2 partner DSS1. Biochemical, structural, and in vivo analyses reveal that DSS1 allows the BRCA2-DSS1 complex to physically and functionally interact with RPA. Mechanistically, DSS1 acts as a DNA mimic to attenuate the affinity of RPA for ssDNA. A mutation in the solvent-exposed acidic domain of DSS1 compromises the efficacy of RPA-RAD51 exchange. Thus, by targeting RPA and mimicking DNA, DSS1 functions with BRCA2 in a two-component homologous recombination mediator complex in genome maintenance and tumor suppression. Our findings may provide a paradigm for understanding the roles of DSS1 in other biological processes.

Indexed as

Homologous RecombinationAmino Acid SubstitutionBRCA2 ProteinBreast NeoplasmsCell LineFemaleHeLa CellsHumansModels, BiologicalMolecular MimicryMutagenesis, Site-DirectedNuclear Magnetic Resonance, BiomolecularProteasome Endopeptidase ComplexProtein SubunitsRad51 RecombinaseRecombinant ProteinsBRCA2 ProteinBRCA2 protein, humanProteasome Endopeptidase ComplexProtein SubunitsRAD51 protein, humanRad51 RecombinaseRecombinant ProteinsReplication Protein ARPA1 protein, humanSEM1 protein, human

Identifiers

PMID26145171
PMCPMC4506714
OpenAlexW1521943738

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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.