ArticleThe Journal of cell biology2016
TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity.
Article in The Journal of cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03251872 (Olaparib for Pulmonary Arterial Hypertension), which is not on this map. Cited by 52 papers.
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.
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.
Olaparib for Pulmonary Arterial Hypertension: a Pilot Clinical Study
Who cites it
52 citing papers in PubMed, 85 citations in OpenAlex.
- DNA end-resection is stimulated by an interaction between BRCA1 exon 11 and TOPBP1.EMBO reports · 2026Article
- Development of a structurally distinct TopBP1 inhibitor that enhances PARP blockade and reverses osimertinib resistance.Science advances · 2026Article
- Molecular landscape and clinical translation of DNA damage response alterations in solid tumors: A pan-cancer perspective on precision oncology.Neoplasia (New York, N.Y.) · 2026Review
- TOPBP1-PLK1 interaction preserves genome integrity during mitosis.Nucleic acids research · 2026Article
- Fragment-based discovery of TopBP1 inhibitors integrated with AI-driven molecular docking.Magnetic resonance letters · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Potent synthetic lethality between PLK1 and EYA family inhibitors in tumors of the central and peripheral nervous systems.Genes & development · 2026Article
- Mutant p53 variants differentially impact replication initiation and activate cGAS-STING to affect immune checkpoint inhibition.Communications biology · 2025Article
- HSF1 remodels mitochondrial biogenesis and function in cancer cells via TIMM17A.bioRxiv : the preprint server for biology · 2025Article
- TOPBP1 as a potential predictive biomarker for enhanced combinatorial efficacy of olaparib and AZD6738 in PDAC.Cell & bioscience · 2025Article
- Defective Homologous Recombination Repair By Up-Regulating Lnc-HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The protein phosphatase EYA4 promotes homologous recombination (HR) through dephosphorylation of tyrosine 315 on RAD51.Nucleic acids research · 2024Article
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- A small-molecule inhibitor of TopBP1 exerts anti-MYC activity and synergy with PARP inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Pre-rRNA Facilitates TopBP1-Mediated DNA Double-Strand Break Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- NBS1 binds directly to TOPBP1 via disparate interactions between the NBS1 BRCT1 domain and the TOPBP1 BRCT1 and BRCT2 domains.DNA repair · 2023Article
- PARP Inhibitors and Proteins Interacting with SLX4.Cancers · 2023Review
- The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment.Journal of hematology & oncology · 2022Review
- CRISPR/Cas9‑induced saturated mutagenesis identifiesMolecular medicine reports · 2022Article
- Targeting Replication Stress Response Pathways to Enhance Genotoxic Chemo- and Radiotherapy.Molecules (Basel, Switzerland) · 2022Review
Corrections and comments
- Commented on by
Authors and funding
15 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Topoisomerase IIβ-binding protein 1 (TOPBP1) participates in DNA replication and DNA damage response; however, its role in DNA repair and relevance for human cancer remain unclear. Here, through an unbiased small interfering RNA screen, we identified and validated TOPBP1 as a novel determinant whose loss sensitized human cells to olaparib, an inhibitor of poly(ADP-ribose) polymerase. We show that TOPBP1 acts in homologous recombination (HR) repair, impacts olaparib response, and exhibits aberrant patterns in subsets of human ovarian carcinomas. TOPBP1 depletion abrogated RAD51 loading to chromatin and formation of RAD51 foci, but without affecting the upstream HR steps of DNA end resection and RPA loading. Furthermore, TOPBP1 BRCT domains 7/8 are essential for RAD51 foci formation. Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51 at serine 14, a modification required for RAD51 recruitment to chromatin. Overall, our results provide mechanistic insights into TOPBP1's role in HR, with potential clinical implications for cancer treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.