ArticleLife science alliance2018
Specificity for deubiquitination of monoubiquitinated FANCD2 is driven by the N-terminus of USP1.
Article in Life science alliance, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Disrupting the USP1-UAF1 deubiquitinase complex: a master regulator of replication stress and frontier target in cancer therapy.Medical oncology (Northwood, London, England) · 2026Review
- Survivin Is a Central Mediator of Cell Proliferation in HPV-Negative Head and Neck Squamous Cell Carcinoma.Cancers · 2025Article
- USP1 inhibition: A journey from target discovery to clinical translation.Pharmacology & therapeutics · 2025Review
- Characterization of TNG348: A Selective, Allosteric USP1 Inhibitor That Synergizes with PARP Inhibitors in Tumors with Homologous Recombination Deficiency.Molecular cancer therapeutics · 2025Article
- Emerging frontiers in protein structure prediction following the AlphaFold revolution.Journal of the Royal Society, Interface · 2025Review
- Structural and Biochemical Insights into the Mechanism of Action of the Clinical USP1 Inhibitor, KSQ-4279.Journal of medicinal chemistry · 2024Article
- Deciphering the role of post-translational modifications in fanconi anemia proteins and their influence on tumorigenesis.Cancer gene therapy · 2024Review
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- Structural and biochemical basis of interdependent FANCI-FANCD2 ubiquitination.The EMBO journal · 2023Article
- Cryo-EM reveals a mechanism of USP1 inhibition through a cryptic binding site.Science advances · 2022Article
- Insert L1 is a central hub for allosteric regulation of USP1 activity.EMBO reports · 2021Article
- Structural basis of FANCD2 deubiquitination by USP1-UAF1.Nature structural & molecular biology · 2021Article
- Structural insight into FANCI-FANCD2 monoubiquitination.Essays in biochemistry · 2020Review
- Differential functions of FANCI and FANCD2 ubiquitination stabilize ID2 complex on DNA.EMBO reports · 2020Article
- Allosteric mechanism for site-specific ubiquitination of FANCD2.Nature chemical biology · 2020Article
- Preparation and purification of mono-ubiquitinated proteins using Avi-tagged ubiquitin.PloS one · 2020Article
- Fanconi anemia pathway as a prospective target for cancer intervention.Cell & bioscience · 2020Review
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Authors and funding
4 authors.
Funding
Abstract
The Fanconi anemia pathway for DNA interstrand crosslink repair and the translesion synthesis pathway for DNA damage tolerance both require cycles of monoubiquitination and deubiquitination. The ubiquitin-specific protease-1 (USP1), in complex with USP1-associated factor 1, regulates multiple DNA repair pathways by deubiquitinating monoubiquitinated Fanconi anemia group D2 protein (FANCD2), Fanconi anemia group I protein (FANCI), and proliferating cell nuclear antigen (PCNA). Loss of USP1 activity gives rise to chromosomal instability. Whereas many USPs hydrolyse ubiquitin-ubiquitin linkages, USP1 targets ubiquitin-substrate conjugates at specific sites. The molecular basis of USP1's specificity for multiple substrates is poorly understood. Here, we reconstitute deubiquitination of purified monoubiquitinated FANCD2, FANCI, and PCNA and show that molecular determinants for substrate deubiquitination by USP1 reside within the highly conserved and extended N-terminus. We found that the N-terminus of USP1 harbours a FANCD2-specific binding sequence required for deubiquitination of K561 on FANCD2. In contrast, the N-terminus is not required for direct PCNA or FANCI deubiquitination. Furthermore, we show that the N-terminus of USP1 is sufficient to engineer specificity in a more promiscuous USP.
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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.