ArticleNature chemical biology2024
UFL1 triggers replication fork degradation by MRE11 in BRCA1/2-deficient cells.
Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- Narrative review-the emerging role, functions, and mechanisms of UFMylation in cancers.Translational cancer research · 2026Review
- Exploring the potential involvement of UFSP2 in spindle assembly checkpoint regulation in breast cancer.Molecular biology reports · 2026Article
- Systematic discovery of UFM1 receptors reveals a regulatory module in DNA repair directing non-homologous end-joining.Nature communications · 2026Article
- The mechanistic basis and cellular functions of UFMylation.Nature reviews. Molecular cell biology · 2026Review
- UFMylation of Pyruvate Dehydrogenase Regulates Mitochondrial Metabolism.bioRxiv : the preprint server for biology · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- The UFL1-AKT positive feedback loop promotes breast cancer progression by enhancing lipid synthesis.Nature communications · 2026Article
- Loss of UFL1 confers enzalutamide resistance of prostate tumors by regulating METTL16-mediated m6A modification of EEF1A1 mRNA.International journal of biological sciences · 2026Article
- Identifying of Ubiquitin-Fold Modifier 1 as a Potential Prognostic Biomarker for Unresectable Pancreatic Cancer by Proteomics Analysis.Cancer management and research · 2026Article
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
- UFMylation System: Biological Functions, Molecular Mechanisms, Diseases, and Drug Discovery.MedComm · 2025Review
- Akt-phosphorylated UFL1 UFMylates ArpC4 to promote metastasis.Nature structural & molecular biology · 2025Article
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- Novel clinical potential of poly (ADP‑ribose) polymerase inhibitors in triple‑negative breast cancer: Mechanistic insights and clinical applications (Review).Oncology letters · 2025Review
- Multifaceted roles of UFMylation in health and disease.Acta pharmacologica Sinica · 2025Review
- The emerging roles of UFMylation in the modulation of immune responses.Clinical and translational medicine · 2024Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
The stabilization of stalled forks has emerged as a crucial mechanism driving resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient tumors. Here, we identify UFL1, a UFM1-specific E3 ligase, as a pivotal regulator of fork stability and the response to PARP inhibitors in BRCA1/2-deficient cells. On replication stress, UFL1 localizes to stalled forks and catalyzes the UFMylation of PTIP, a component of the MLL3/4 methyltransferase complex, specifically at lysine 148. This modification facilitates the assembly of the PTIP-MLL3/4 complex, resulting in the enrichment of H3K4me1 and H3K4me3 at stalled forks and subsequent recruitment of the MRE11 nuclease. Consequently, loss of UFL1, disruption of PTIP UFMylation or overexpression of the UFM1 protease UFSP2 protects nascent DNA strands from extensive degradation and confers resistance to PARP inhibitors in BRCA1/2-deficient cells. These findings provide mechanistic insights into the processes underlying fork instability in BRCA1/2-deficient cells and offer potential therapeutic avenues for the treatment of BRCA1/2-deficient tumors.
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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 Socratic graph.