ArticleScience advances2021
GRB2 enforces homology-directed repair initiation by MRE11.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- Taming Mre11-Rad50 at Telomeres: Convergent Strategies for Chromosome-End Protection Across Evolution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- PARG Governs a PARylation-Ubiquitination Toggle that Stabilizes RAD51AP1 to Drive Homologous Recombination-Mediated Chemoresistance.Cancer research · 2026Article
- Engineering a Stable Grb2 Monomer: The W60A Mutation Disrupts Dimerization but Preserves Structural Integrity.ACS omega · 2026Article
- Poly(ADP-ribose) glycohydrolase enforces p21 degradation via dePARylation to promote gastric cancer progression.The Journal of clinical investigation · 2026Article
- HP1β recruits RING1A to ubiquitinate histone H2A for BRCA1-mediated resection of double-stand breaks.iScience · 2026Article
- RBBP6 and cancer: from molecular mechanisms to clinical implications.Frontiers in oncology · 2026Review
- PVC Nanoplastics Exposure Exacerbates Asthma through R-Loop Accumulation and Subsequent STING Activation in Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Evaluating log odds of positive lymph nodes as a prognostic tool in differentiated gastric cancer: A retrospective study.World journal of gastroenterology · 2025Article
- RNA sculpting by the primordial Helix-clasp-Helix-Strand-Loop (HcH-SL) motif enforces chemical recognition enabling diverse KH domain functions.The Journal of biological chemistry · 2025Review
- RBBP6 maintains glioblastoma stem cells through CPSF3-dependent alternative polyadenylation.Cell discovery · 2024Article
- GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer.Nature communications · 2024Article
- The Configuration of GRB2 in Protein Interaction and Signal Transduction.Biomolecules · 2024Review
- Olaparib combined with CDK12-IN-3 to promote genomic instability and cell death in ovarian cancer.International journal of biological sciences · 2024Article
- A goldilocks computational protocol for inhibitor discovery targeting DNA damage responses including replication-repair functions.Frontiers in molecular biosciences · 2024Article
- PRL1 and PRL3 promote macropinocytosis via its lipid phosphatase activity.Theranostics · 2024Article
- Novobiocin blocks nucleic acid binding to Polθ and inhibits stimulation of its ATPase activity.Nucleic acids research · 2023Article
- Dynamics of the DYNLL1-MRE11 complex regulate DNA end resection and recruitment of Shieldin to DSBs.Nature structural & molecular biology · 2023Article
- Regulation of microRNA expression by the adaptor protein GRB2.Scientific reports · 2023Article
- Article
- A scanning-to-incision switch in TFIIH-XPG induced by DNA damage licenses nucleotide excision repair.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
DNA double-strand break (DSB) repair is initiated by MRE11 nuclease for both homology-directed repair (HDR) and alternative end joining (Alt-EJ). Here, we found that GRB2, crucial to timely proliferative RAS/MAPK pathway activation, unexpectedly forms a biophysically validated GRB2-MRE11 (GM) complex for efficient HDR initiation. GRB2-SH2 domain targets the GM complex to phosphorylated H2AX at DSBs. GRB2 K109 ubiquitination by E3 ubiquitin ligase RBBP6 releases MRE11 promoting HDR. RBBP6 depletion results in prolonged GM complex and HDR defects. GRB2 knockout increased MRE11-XRCC1 complex and Alt-EJ. Reconstitution with separation-of-function GRB2 mutant caused HDR deficiency and synthetic lethality with PARP inhibitor. Cell and cancer genome analyses suggest biomarkers of low GRB2 for noncanonical HDR deficiency and high MRE11 and GRB2 expression for worse survival in HDR-proficient patients. These findings establish GRB2's role in binding, targeting, and releasing MRE11 to promote efficient HDR over Alt-EJ DSB repair, with implications for genome stability and cancer biology.
Identifiers
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Registered trials
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.