ArticleNature chemical biology2020
Allosteric mechanism for site-specific ubiquitination of FANCD2.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Tuning ubiquitin transfer by RING E3 ubiquitin ligases through the linchpin residue.Life science alliance · 2025Article
- Capsaicin Inhibits Ferroptosis through Facilitating SYVN1-Mediated Ubiquitination and Degradation of ACSL4.Journal of agricultural and food chemistry · 2025Article
- Targeting E3 ubiquitin ligases: a new frontier in idiopathic pulmonary fibrosis treatment.Frontiers in immunology · 2025Review
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- Research progress on the fanconi anemia signaling pathway in non-obstructive azoospermia.Frontiers in endocrinology · 2024Review
- Trim-Away ubiquitinates and degrades lysine-less and N-terminally acetylated substrates.Nature communications · 2023Article
- Diverse roles of UBE2T in cancer (Review).Oncology reports · 2023Article
- 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
- Unveiling the Essential Role of Arkadia's Non-RING Elements in the Ubiquitination Process.International journal of molecular sciences · 2022Article
- Site-specific ubiquitination: Deconstructing the degradation tag.Current opinion in structural biology · 2022Review
- Functional conservation and divergence of the helix-turn-helix motif of E2 ubiquitin-conjugating enzymes.The EMBO journal · 2022Article
- Cyclin-Dependent Kinase-Mediated Phosphorylation of FANCD2 Promotes Mitotic Fidelity.Molecular and cellular biology · 2021Article
- Structural basis of FANCD2 deubiquitination by USP1-UAF1.Nature structural & molecular biology · 2021Article
- Tools for Decoding Ubiquitin Signaling in DNA Repair.Frontiers in cell and developmental biology · 2021Review
- Differential functions of FANCI and FANCD2 ubiquitination stabilize ID2 complex on DNA.EMBO reports · 2020Article
- Characterization of FANCL variants observed in patient cancer cells.Bioscience reports · 2020Article
- Rewiring E2 enzymes.Nature chemical biology · 2020Article
- Preparation and purification of mono-ubiquitinated proteins using Avi-tagged ubiquitin.PloS one · 2020Article
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6 authors at 3 institutions in 1 country.
Funding
Abstract
DNA-damage repair is implemented by proteins that are coordinated by specialized molecular signals. One such signal in the Fanconi anemia (FA) pathway for the repair of DNA interstrand crosslinks is the site-specific monoubiquitination of FANCD2 and FANCI. The signal is mediated by a multiprotein FA core complex (FA-CC) however, the mechanics for precise ubiquitination remain elusive. We show that FANCL, the RING-bearing module in FA-CC, allosterically activates its cognate ubiqutin-conjugating enzyme E2 UBE2T to drive site-specific FANCD2 ubiquitination. Unlike typical RING E3 ligases, FANCL catalyzes ubiquitination by rewiring the intraresidue network of UBE2T to influence the active site. Consequently, a basic triad unique to UBE2T engages a structured acidic patch near the target lysine on FANCD2. This three-dimensional complementarity, between the E2 active site and substrate surface, induced by FANCL is central to site-specific monoubiquitination in the FA pathway. Furthermore, the allosteric network of UBE2T can be engineered to enhance FANCL-catalyzed FANCD2-FANCI di-monoubiquitination without compromising site specificity.
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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.