ArticleNucleic acids research2019
The WD40 domain of FBXW7 is a poly(ADP-ribose)-binding domain that mediates the early DNA damage response.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Global patterns of mutational profiles in biliary tract cancer.Journal of hepatology · 2026Article
- TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer.Nature communications · 2026Article
- Bioinformatics analysis and clinical validation identifyTranslational andrology and urology · 2026Article
- Finely-tuned regulator of DNA repair: FBXW7-185aa may modulate glioblastoma radiosensitization and the tumor immune microenvironment.Translational oncology · 2026Article
- Therapy-associated mutagenesis at CTCF binding sites is shaped by chromatin context and DNA repair capacity.bioRxiv : the preprint server for biology · 2026Article
- FBXW7 metabolic reprogramming inhibits the development of colon cancer by down-regulating the activity of arginine/mToR pathways.PloS one · 2025Article
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- RNF166 promotes colorectal cancer progression by recognizing and destabilizing poly-ADP-ribosylated angiomotins.Cell death & disease · 2024Article
- FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects.Frontiers in pharmacology · 2024Review
- Revolutionizing DNA repair research and cancer therapy with CRISPR-Cas screens.Nature reviews. Molecular cell biology · 2023Review
- Different miRNAs Related toInternational journal of molecular sciences · 2023Article
- A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer.International journal of molecular sciences · 2023Article
- DNA Double-Strand Break-Related Competitive Endogenous RNA Network of Noncoding RNA in Bovine Cumulus Cells.Genes · 2023Article
- In silico analysis of a Skp1 protein homolog from the human pathogenJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022Article
- Clinical significance of FBXW7 loss of function in human cancers.Molecular cancer · 2022Review
- Modified Adenosines Sensitize Glioblastoma Cells to Temozolomide by Affecting DNA Methyltransferases.Frontiers in pharmacology · 2022Article
- Chromatin Ubiquitination Guides DNA Double Strand Break Signaling and Repair.Frontiers in cell and developmental biology · 2022Review
- Complete response to neoadjuvant chemoradiotherapy in rectal cancer is associated with RAS/AKT mutations and high tumour mutational burden.Radiation oncology (London, England) · 2021Article
- Functional Roles of Poly(ADP-Ribose) in Stress Granule Formation and Dynamics.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
FBXW7, a classic tumor suppressor, is a substrate recognition subunit of the Skp1-cullin-F-box (SCF) ubiquitin ligase that targets oncoproteins for ubiquitination and degradation. We recently found that FBXW7 is recruited to DNA damage sites to facilitate nonhomologous end-joining (NHEJ). The detailed underlying molecular mechanism, however, remains elusive. Here we report that the WD40 domain of FBXW7, which is responsible for substrate binding and frequently mutated in human cancers, binds to poly(ADP-ribose) (PAR) immediately following DNA damage and mediates rapid recruitment of FBXW7 to DNA damage sites, whereas ATM-mediated FBXW7 phosphorylation promotes its retention at DNA damage sites. Cancer-associated arginine mutations in the WD40 domain (R465H, R479Q and R505C) abolish both FBXW7 interaction with PAR and recruitment to DNA damage sites, causing inhibition of XRCC4 polyubiquitination and NHEJ. Furthermore, inhibition or silencing of poly(ADP-ribose) polymerase 1 (PARP1) inhibits PAR-mediated recruitment of FBXW7 to the DNA damage sites. Taken together, our study demonstrates that the WD40 domain of FBXW7 is a novel PAR-binding motif that facilitates early recruitment of FBXW7 to DNA damage sites for subsequent NHEJ repair. Abrogation of this ability seen in cancer-derived FBXW7 mutations provides a molecular mechanism for defective DNA repair, eventually leading to genome instability.
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.