ArticleNucleic acids research2012
Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in the human RAD6A-RAD18 ternary complex.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Overlapping RAD18-and DNA-binding interfaces in DNA polymerase η contribute to UV-induced DNA damage tolerance.The Journal of biological chemistry · 2026Article
- USP1 inhibition promotes RAD18-dependent PCNA degradation and BRCA1 synthetic lethality.bioRxiv : the preprint server for biology · 2026Article
- Phosphorylation by CDK1 switches the function of the human SLX4 SAP domain from DNA binding to MUS81 binding.Nucleic acids research · 2026Article
- Progress for RAD18's mechanism in breast cancer radioresistant.Open life sciences · 2026Review
- RAD18 methylation by the methyltransferase SETD6 attenuates DNA breaks.Scientific reports · 2025Article
- RAD18 directs DNA double-strand break repair by homologous recombination to post-replicative chromatin.Nucleic acids research · 2024Article
- The Role of Ubiquitination in Osteosarcoma Development and Therapies.Biomolecules · 2024Review
- Structural basis for RAD18 regulation by MAGEA4 and its implications for RING ubiquitin ligase binding by MAGE family proteins.The EMBO journal · 2024Article
- Novel mechanisms for the removal of strong replication-blocking HMCES- and thiazolidine-DNA adducts in humans.Nucleic acids research · 2023Article
- A series of xanthenes inhibiting Rad6 function and Rad6-Rad18 interaction in the PCNA ubiquitination cascade.iScience · 2022Article
- The Zn-finger of Saccharomyces cerevisiae Rad18 and its adjacent region mediate interaction with Rad5.G3 (Bethesda, Md.) · 2021Article
- PCNA Monoubiquitination Is Regulated by Diffusion of Rad6/Rad18 Complexes along RPA Filaments.Biochemistry · 2020Article
- Review
- How to Inactivate Human Ubiquitin E3 Ligases by Mutation.Frontiers in cell and developmental biology · 2020Review
- Replication protein A dynamically regulates monoubiquitination of proliferating cell nuclear antigen.The Journal of biological chemistry · 2019Article
- Preferential digestion of PCNA-ubiquitin and p53-ubiquitin linkages by USP7 to remove polyubiquitin chains from substrates.The Journal of biological chemistry · 2019Article
- Regulation of HLTF-mediated PCNA polyubiquitination by RFC and PCNA monoubiquitination levels determines choice of damage tolerance pathway.Nucleic acids research · 2018Article
- A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis.Nature communications · 2016Article
- Article
- Different types of interaction between PCNA and PIP boxes contribute to distinct cellular functions of Y-family DNA polymerases.Nucleic acids research · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RAD18, a RING-type ubiquitin ligase (E3) that plays an essential role in post-replication repair, possesses distinct domains named RING, UBZ, SAP and the RAD6-binding domain (R6BD) and forms a dimer. RAD6, an ubiquitin-conjugating enzyme (E2), stably associates with R6BD in the C-terminal portion. In this study, we established a method to distinguish between the two subunits of RAD18 by introduction of different tags, and analyzed mutant complexes. Our results, surprisingly, demonstrate that RAD6A and RAD18 form a ternary complex, RAD6A-(RAD18)(2) and the presence of only one R6BD in the two RAD18 subunits is sufficient for ternary complex formation and the ligase activity. Interestingly, ligase activity of a mutant dimer lacking both R6BDs is not restored even with large amounts of RAD6A added in solution, suggesting a requirement for precise juxtaposition via interaction with R6BD. We further show that mutations in both subunits of either RING or SAP, but not UBZ, strongly reduce ligase activity, although inactivation in only one of two subunits is without effect. These results suggest an asymmetric nature of the two RAD18 subunits in the complex.
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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.