ArticleBiochemistry2020
PCNA Monoubiquitination Is Regulated by Diffusion of Rad6/Rad18 Complexes along RPA Filaments.
Article in Biochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- The Oligomeric State of Rad6-Rad18 and Its Interactions with Translesion Synthesis Proteins.Biomolecules · 2026Article
- USP1 inhibition promotes RAD18-dependent PCNA degradation and BRCA1 synthetic lethality.bioRxiv : the preprint server for biology · 2026Article
- Article
- Fork Reversal Safeguards Epigenetic Inheritance During Replication Stress.Research square · 2026Article
- PCNA encircling primer/template junctions is eliminated by exchange of RPA for Rad51: implications for the interplay between human DNA damage tolerance pathways.Nucleic acids research · 2026Article
- Therapeutic 6-thio-deoxyguanosine inhibits telomere elongation in cancer cells by inducing a non-productive stalled telomerase complex.Nature communications · 2025Article
- Structure of the human CTF18-RFC clamp loader bound to PCNA.bioRxiv : the preprint server for biology · 2025Article
- A human high-fidelity DNA polymerase holoenzyme has a wide range of lesion bypass activities.Nucleic acids research · 2025Article
- The DNA damage tolerance factor Rad5 and telomere replication.Current genetics · 2025Review
- Replicative DNA polymerase epsilon and delta holoenzymes show wide-ranging inhibition at G-quadruplexes in the human genome.Nucleic acids research · 2025Article
- A human high-fidelity DNA polymerase holoenzyme has a wide range of lesion bypass activities.bioRxiv : the preprint server for biology · 2024Article
- Replication protein A dynamically re-organizes on primer/template junctions to permit DNA polymerase δ holoenzyme assembly and initiation of DNA synthesis.Nucleic acids research · 2024Article
- Replication of [AT/TA]Biochemistry · 2024Article
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- Direct, ensemble FRET approaches to monitor transient state kinetics of human DNA polymerase δ holoenzyme assembly and initiation of DNA synthesis.Methods in enzymology · 2024Article
- Replication of [AT/TA]bioRxiv : the preprint server for biology · 2023Article
- Mechanistic insight into AP-endonuclease 1 cleavage of abasic sites at stalled replication fork mimics.Nucleic acids research · 2023Article
- Review
- Impacts of arsenic on Rad18 and translesion synthesis.Toxicology and applied pharmacology · 2022Article
- Tracking of progressing human DNA polymerase δ holoenzymes reveals distributions of DNA lesion bypass activities.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Translesion DNA synthesis (TLS) enables DNA replication through damaging modifications to template DNA and requires monoubiquitination of the proliferating cell nuclear antigen (PCNA) sliding clamp by the Rad6/Rad18 complex. This posttranslational modification is critical to cell survival following exposure to DNA-damaging agents and is tightly regulated to restrict TLS to damaged DNA. Replication protein A (RPA), the major single-strand DNA (ssDNA) binding protein complex, forms filaments on ssDNA exposed at TLS sites and plays critical yet undefined roles in regulating PCNA monoubiquitination. Here, we utilize kinetic assays and single-molecule FRET microscopy to monitor PCNA monoubiquitination and Rad6/Rad18 complex dynamics on RPA filaments, respectively. Results reveal that a Rad6/Rad18 complex is recruited to an RPA filament via Rad18·RPA interactions and randomly translocates along the filament. These translocations promote productive interactions between the Rad6/Rad18 complex and the resident PCNA, significantly enhancing monoubiquitination. These results illuminate critical roles of RPA in the specificity and efficiency of PCNA monoubiquitination and represent, to the best of our knowledge, the first example of ATP-independent translocation of a protein complex along a protein filament.
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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.