ArticleNucleic acids research2012
En bloc transfer of polyubiquitin chains to PCNA in vitro is mediated by two different human E2-E3 pairs.
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 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- HLTF resolves G4s and promotes G4-induced replication fork slowing to maintain genome stability.Molecular cell · 2024Article
- Adaptive use of error-prone DNA polymerases provides flexibility in genome replication during tumorigenesis.Cancer science · 2024Review
- The levels of p53 govern the hierarchy of DNA damage tolerance pathway usage.Nucleic acids research · 2024Article
- Degradation of helicase-like transcription factor (HLTF) by β-TrCP promotes hepatocarcinogenesis via activation of the p62/mTOR axis.Journal of molecular cell biology · 2023Article
- HLTF promotes hepatocellular carcinoma progression by enhancing SRSF1 stability and activating ERK/MAPK pathway.Oncogenesis · 2023Article
- Article
- Redox-sensitive E2 Rad6 controls cellular response to oxidative stress via K63-linked ubiquitination of ribosomes.Cell reports · 2022Article
- Rad5 and Its Human Homologs, HLTF and SHPRH, Are Novel Interactors of Mismatch Repair.Frontiers in cell and developmental biology · 2022Article
- Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy.International journal of molecular sciences · 2021Review
- Structural basis for the multi-activity factor Rad5 in replication stress tolerance.Nature communications · 2021Article
- Mechanisms of direct replication restart at stressed replisomes.DNA repair · 2020Review
- Effects of chain length and geometry on the activation of DNA damage bypass by polyubiquitylated PCNA.Nucleic acids research · 2020Article
- Helicase-Like Transcription Factor HLTF and E3 Ubiquitin Ligase SHPRH Confer DNA Damage Tolerance through Direct Interactions with Proliferating Cell Nuclear Antigen (PCNA).International journal of molecular sciences · 2020Article
- Unanchored Ubiquitin Chains, Revisited.Frontiers in cell and developmental biology · 2020Review
- Replication Fork Remodeling and Therapy Escape in DNA Damage Response-Deficient Cancers.Frontiers in oncology · 2020Review
- Preferential digestion of PCNA-ubiquitin and p53-ubiquitin linkages by USP7 to remove polyubiquitin chains from substrates.The Journal of biological chemistry · 2019Article
- Enzymatic Logic of Ubiquitin Chain Assembly.Frontiers in physiology · 2019Review
- Regulation of HLTF-mediated PCNA polyubiquitination by RFC and PCNA monoubiquitination levels determines choice of damage tolerance pathway.Nucleic acids research · 2018Article
- Ubiquitylation at the Fork: Making and Breaking Chains to Complete DNA Replication.International journal of molecular sciences · 2018Review
- Expression and Regulation of Deubiquitinase-Resistant, Unanchored Ubiquitin Chains in Drosophila.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Post-replication DNA repair in eukaryotes is regulated by ubiquitination of proliferating cell nuclear antigen (PCNA). Monoubiquitination catalyzed by RAD6-RAD18 (an E2-E3 complex) stimulates translesion DNA synthesis, whereas polyubiquitination, promoted by additional factors such as MMS2-UBC13 (a UEV-E2 complex) and HLTF (an E3 ligase), leads to template switching in humans. Here, using an in vitro ubiquitination reaction system reconstituted with purified human proteins, we demonstrated that PCNA is polyubiquitinated predominantly via en bloc transfer of a pre-formed ubiquitin (Ub) chain rather than by extension of the Ub chain on monoubiquitinated PCNA. Our results support a model in which HLTF forms a thiol-linked Ub chain on UBC13 (UBC13∼Ubn) and then transfers the chain to RAD6∼Ub, forming RAD6∼Ubn+1. The resultant Ub chain is subsequently transferred to PCNA by RAD18. Thus, template switching may be promoted under certain circumstances in which both RAD18 and HLTF are coordinately recruited to sites of stalled replication.
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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.