ArticleNature communications2022
USP1-trapping lesions as a source of DNA replication stress and genomic instability.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- GLS1 Orchestrates Exosome-Mediated Tumor-Endothelial Communication to Facilitate Angiogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Disrupting the USP1-UAF1 deubiquitinase complex: a master regulator of replication stress and frontier target in cancer therapy.Medical oncology (Northwood, London, England) · 2026Review
- NRF1 Transcriptionally Regulates USP1-Mediated Deubiquitination of AURKA to Facilitate Osteosarcoma Progression.Molecular biotechnology · 2026Article
- Biochemical and Comparative Proteomic Analyses Delineate the Anti-Ovarian Carcinogenic Roles of Modified Calycosin.Food science & nutrition · 2026Article
- SLFN11 counteracts the RFWD3-PRIMPOL DNA damage tolerance axis to restrain gapped DNA synthesis in response to replication stress.Nature communications · 2025Article
- Mechanistic insights into the monotherapy and combination potential of FEN1 inhibition in cancer therapy.Nucleic acids research · 2025Article
- USP1 inhibition: A journey from target discovery to clinical translation.Pharmacology & therapeutics · 2025Review
- ZC3H4 safeguards genome integrity by preventing transcription-replication conflicts at noncoding RNA loci.Science advances · 2025Article
- USP1 inhibits influenza A and B virus replication in MDCK cells by mediating RIG-I deubiquitination.Cellular and molecular life sciences : CMLS · 2025Article
- Inherited deficiency of DIAPH1 identifies a DNA double strand break repair pathway regulated by γ-actin.Nature communications · 2025Article
- Characterization of TNG348: A Selective, Allosteric USP1 Inhibitor That Synergizes with PARP Inhibitors in Tumors with Homologous Recombination Deficiency.Molecular cancer therapeutics · 2025Article
- Article
- The other side of the coin: protein deubiquitination by Ubiquitin-Specific Protease 1 in cancer progression and therapy.Future medicinal chemistry · 2025Review
- Glucose limitation protects cancer cells from apoptosis induced by pyrimidine restriction and replication inhibition.Nature metabolism · 2024Article
- USP1 deubiquitinates PARP1 to regulate its trapping and PARylation activity.Science advances · 2024Article
- Single-Stranded DNA Gap Accumulation Is a Functional Biomarker for USP1 Inhibitor Sensitivity.Cancer research · 2024Article
- The USP1 Inhibitor KSQ-4279 Overcomes PARP Inhibitor Resistance in Homologous Recombination-Deficient Tumors.Cancer research · 2024Article
- Therapeutic Targeting of the GLS1-c-Myc Positive Feedback Loop Suppresses Glutaminolysis and Inhibits Progression of Head and Neck Cancer.Cancer research · 2024Article
- Structural and Biochemical Insights into the Mechanism of Action of the Clinical USP1 Inhibitor, KSQ-4279.Journal of medicinal chemistry · 2024Article
- Comprehensive Review of Chronic Stress Pathways and the Efficacy of Behavioral Stress Reduction Programs (BSRPs) in Managing Diseases.International journal of environmental research and public health · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The deubiquitinase USP1 is a critical regulator of genome integrity through the deubiquitylation of Fanconi Anemia proteins and the DNA replication processivity factor, proliferating cell nuclear antigen (PCNA). Uniquely, following UV irradiation, USP1 self-inactivates through autocleavage, which enables its own degradation and in turn, upregulates PCNA monoubiquitylation. However, the functional role for this autocleavage event during physiological conditions remains elusive. Herein, we discover that cells harboring an autocleavage-defective USP1 mutant, while still able to robustly deubiquitylate PCNA, experience more replication fork-stalling and premature fork termination events. Using super-resolution microscopy and live-cell single-molecule tracking, we show that these defects are related to the inability of this USP1 mutant to be properly recycled from sites of active DNA synthesis, resulting in replication-associated lesions. Furthermore, we find that the removal of USP1 molecules from DNA is facilitated by the DNA-dependent metalloprotease Spartan to counteract the cytotoxicity caused by "USP1-trapping". We propose a utility of USP1 inhibitors in cancer therapy based on their ability to induce USP1-trapping lesions and consequent replication stress and genomic instability in cancer cells, similar to how non-covalent DNA-protein crosslinks cause cytotoxicity by imposing steric hindrances upon proteins involved in DNA transactions.
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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.