ArticleMolecular cell2021
The ubiquitin ligase RFWD3 is required for translesion DNA synthesis.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 82 citations in OpenAlex.
- DPP9 modulates RPA1 stability and temozolomide sensitivity through RFWD3 Nuclear localization in glioma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- A ubiquitin chain-feeding mechanism for BRCA1-A.Nature communications · 2026Article
- SLFN11 counteracts the RFWD3-PRIMPOL DNA damage tolerance axis to restrain gapped DNA synthesis in response to replication stress.Nature communications · 2025Article
- The Fanconi anemia pathway repairs colibactin-induced DNA interstrand cross-links.Nature communications · 2025Article
- DNA polymerase kappa is the primary translesion synthesis polymerase for aldehyde ICLs.Nucleic acids research · 2025Article
- Leading and lagging strand abasic sites differentially affect vertebrate replisome progression but involve analogous bypass mechanisms.Nucleic acids research · 2025Article
- Allosteric activation of the SPRTN protease by ubiquitin maintains genome stability.Nature communications · 2025Article
- The dual ubiquitin binding mode of SPRTN secures rapid spatiotemporal proteolysis of DNA-protein crosslinks.Nucleic acids research · 2025Article
- Elucidating the genetic mechanisms governing cytosine base editing outcomes through CRISPRi screens.Nature communications · 2025Article
- Article
- RFWD3 Reprograms Nucleotide Metabolism Through PHGDH to Induce Chemoresistance In Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Estrogen Promotes Endometrial Cancer Development by Modulating ZNF626, SLK, and RFWD3 Gene Expression and Inducing Immune Inflammatory Changes.Biomedicines · 2025Article
- Catalytic and noncatalytic functions of DNA polymerase κ in translesion DNA synthesis.Nature structural & molecular biology · 2025Article
- PCNA-binding activity separates RNF168 functions in DNA replication and DNA double-stranded break signaling.Nucleic acids research · 2024Article
- The USP1 Inhibitor KSQ-4279 Overcomes PARP Inhibitor Resistance in Homologous Recombination-Deficient Tumors.Cancer research · 2024Article
- Electro-elution-based purification of covalent DNA-protein cross-links.Nature protocols · 2024Review
- The cullin Rtt101 promotes ubiquitin-dependent DNA-protein crosslink repair across the cell cycle.Nucleic acids research · 2024Article
- Repair of genomic interstrand crosslinks.DNA repair · 2024Review
- PARP1-dependent DNA-protein crosslink repair.Nature communications · 2024Article
- E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.The Biochemical journal · 2024Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lesions on DNA uncouple DNA synthesis from the replisome, generating stretches of unreplicated single-stranded DNA (ssDNA) behind the replication fork. These ssDNA gaps need to be filled in to complete DNA duplication. Gap-filling synthesis involves either translesion DNA synthesis (TLS) or template switching (TS). Controlling these processes, ubiquitylated PCNA recruits many proteins that dictate pathway choice, but the enzymes regulating PCNA ubiquitylation in vertebrates remain poorly defined. Here we report that the E3 ubiquitin ligase RFWD3 promotes ubiquitylation of proteins on ssDNA. The absence of RFWD3 leads to a profound defect in recruitment of key repair and signaling factors to damaged chromatin. As a result, PCNA ubiquitylation is inhibited without RFWD3, and TLS across different DNA lesions is drastically impaired. We propose that RFWD3 is an essential coordinator of the response to ssDNA gaps, where it promotes ubiquitylation to drive recruitment of effectors of PCNA ubiquitylation and DNA damage bypass.
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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.