Evidence map›Paper›PMID 38459011›Full record

ArticleNature communications2024

GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer.

Zu Ye, Shengfeng Xu, Yin Shi, Xueqian Cheng, Yuan Zhang, Sunetra Roy, Sarita Namjoshi, Michael A Longo, Todd M Link, Katharina Schlacher and 5 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
8.5field-weighted citation impact, top 2% 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

27 citing papers in PubMed, 31 citations in OpenAlex.

  1. Trial
  2. DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026
    Article
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  6. Therapeutic delivery of albumin-binding siRNA targeting IRS2 to diverse cell types reduces mammary tumor growth.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
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  10. Review
  11. 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

15 authors at 1 institution in 2 countries.

Zu YeDepartments of Molecular and Cellular Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Shengfeng XuDepartment of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Yin ShiDepartment of Biochemistry, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Xueqian ChengDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Yuan ZhangDepartments of Molecular and Cellular Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Sunetra RoyDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Sarita NamjoshiDepartments of Molecular and Cellular Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Michael A LongoDepartments of Molecular and Cellular Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Todd M LinkDepartments of Molecular and Cellular Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Katharina SchlacherDepartment of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID 0000-0001-7226-6391
Guang PengDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID 0000-0002-4392-1497
Dihua YuDepartments of Molecular and Cellular Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID 0000-0001-6231-9381
Bin WangDepartment of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.ORCID 0000-0003-3352-6992
John A TainerDepartments of Molecular and Cellular Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. JTainer@mdanderson.org.ORCID 0000-0003-1659-2429
Zamal AhmedDepartments of Molecular and Cellular Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. ZAhmed@mdanderson.org.ORCID 0000-0003-3400-6577
The University of Texas MD Anderson Cancer Center · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Mesoscale and Nanoscale Technologies Integrated by Structures for DNA Repair Complexes (MANTIS-DRC)R35CA220430 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI John A. Tainer · 2018 to 2026
$7.6M
Mechanisms of radioresistance and strategies for radiosensitization in ovarian clear cell carcinomaR01CA181663 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Guang Peng · 2016 to 2026
$3.1M
Coordination of DNA repair and transcription by ubiquitin modification at DNA double strand breaksR01CA248088 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WANG, BIN · 2020 to 2024
$1.8M
Mechanism of RAD51C fork protection and environmental carcinogenesisR01ES029680 · NIEHS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SCHLACHER, KATHARINA · 2018 to 2022
$1.8M
PHARMACOLOGICAL MODULATION OF POLY(ADP-RIBOSE) METABOLISMR01CA200231 · NCI · WASHINGTON UNIVERSITY · PI AHMED, ZAMAL, JONES, DARIN E. · 2016 to 2020
$1.7M
Orbitrap Elite High-Resolution Mass Spectrometer for Proteomics and MetabolomicsS10OD012304 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HAWKE, DAVID H · 2013 to 2013
$877k
NCI NIH HHS P01 CA092584NCI NIH HHS R01 CA181663NCI NIH HHS R01 CA200231NCI NIH HHS R01 CA248088NCI NIH HHS R35 CA220430NIEHS NIH HHS R01 ES029680NIH HHS S10 OD012304
6 · The paper itself

Abstract

Growth factor receptor-bound protein 2 (GRB2) is a cytoplasmic adapter for tyrosine kinase signaling and a nuclear adapter for homology-directed-DNA repair. Here we find nuclear GRB2 protects DNA at stalled replication forks from MRE11-mediated degradation in the BRCA2 replication fork protection axis. Mechanistically, GRB2 binds and inhibits RAD51 ATPase activity to stabilize RAD51 on stalled replication forks. In GRB2-depleted cells, PARP inhibitor (PARPi) treatment releases DNA fragments from stalled forks into the cytoplasm that activate the cGAS-STING pathway to trigger pro-inflammatory cytokine production. Moreover in a syngeneic mouse metastatic ovarian cancer model, GRB2 depletion in the context of PARPi treatment reduced tumor burden and enabled high survival consistent with immune suppression of cancer growth. Collective findings unveil GRB2 function and mechanism for fork protection in the BRCA2-RAD51-MRE11 axis and suggest GRB2 as a potential therapeutic target and an enabling predictive biomarker for patient selection for PARPi and immunotherapy combination.

Indexed as

DNA ReplicationNeoplasmsAnimalsDNAGenomic InstabilityGRB2 Adaptor ProteinHumansImmunity, InnateMiceMRE11 Homologue ProteinRad51 RecombinaseDNAGRB2 Adaptor ProteinGRB2 protein, humanGrb2 protein, mouseMRE11 Homologue ProteinRAD51 protein, humanRad51 protein, mouseRad51 Recombinase

Identifiers

PMID38459011
PMCPMC10923831
OpenAlexW4392598631

What Socratic holds

Textmetadata
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 Socratic graph.