ArticleNucleic acids research2018
Regulation of HLTF-mediated PCNA polyubiquitination by RFC and PCNA monoubiquitination levels determines choice of damage tolerance pathway.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Targeting common denominators of DNA damage tolerance mechanisms as therapeutic strategy to cope with dynamic phenotypic changes in triple-negative breast cancer cells.Cell death discovery · 2026Article
- SHPRH together with the Ube2D family of enzymes directly ubiquitinates PCNA at Lys164 in vitro.PloS one · 2026Article
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- The SWI/SNF-related protein SMARCA3 is a histone H3K23 ubiquitin ligase that regulates H3K9me3 in cancer.Molecular cell · 2025Article
- HLTF Promotes the Proliferation of Osteosarcoma Cells and Cisplatin Resistance.Anti-cancer agents in medicinal chemistry · 2025Article
- Adaptive use of error-prone DNA polymerases provides flexibility in genome replication during tumorigenesis.Cancer science · 2024Review
- The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.International journal of molecular sciences · 2023Review
- An inventory of crosstalk between ubiquitination and other post-translational modifications in orchestrating cellular processes.iScience · 2023Review
- Review
- HLTF promotes hepatocellular carcinoma progression by enhancing SRSF1 stability and activating ERK/MAPK pathway.Oncogenesis · 2023Article
- RAD18 opposes transcription-associated genome instability through FANCD2 recruitment.PLoS genetics · 2022Article
- RFWD3 and translesion DNA polymerases contribute to PCNA modification-dependent DNA damage tolerance.Life science alliance · 2022Article
- Monoubiquitination in Homeostasis and Cancer.International journal of molecular sciences · 2022Review
- Genome-wide CRISPR screen identified Rad18 as a determinant of doxorubicin sensitivity in osteosarcoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Active DNA damage eviction by HLTF stimulates nucleotide excision repair.Molecular cell · 2022Article
- Pyroptosis in spinal cord injury.Frontiers in cellular neuroscience · 2022Review
- Structural basis for the multi-activity factor Rad5 in replication stress tolerance.Nature communications · 2021Article
- Eukaryotic clamp loaders and unloaders in the maintenance of genome stability.Experimental & molecular medicine · 2020Review
- Mechanisms of direct replication restart at stressed replisomes.DNA repair · 2020Review
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA-damage tolerance protects cells via at least two sub-pathways regulated by proliferating cell nuclear antigen (PCNA) ubiquitination in eukaryotes: translesion DNA synthesis (TLS) and template switching (TS), which are stimulated by mono- and polyubiquitination, respectively. However, how cells choose between the two pathways remains unclear. The regulation of ubiquitin ligases catalyzing polyubiquitination, such as helicase-like transcription factor (HLTF), could play a role in the choice of pathway. Here, we demonstrate that the ligase activity of HLTF is stimulated by double-stranded DNA via HIRAN domain-dependent recruitment to stalled primer ends. Replication factor C (RFC) and PCNA located at primer ends, however, suppress en bloc polyubiquitination in the complex, redirecting toward sequential chain elongation. When PCNA in the complex is monoubiquitinated by RAD6-RAD18, the resulting ubiquitin moiety is immediately polyubiquitinated by coexisting HLTF, indicating a coupling reaction between mono- and polyubiquitination. By contrast, when PCNA was monoubiquitinated in the absence of HLTF, it was not polyubiquitinated by subsequently recruited HLTF unless all three-subunits of PCNA were monoubiquitinated, indicating that the uncoupling reaction specifically occurs on three-subunit-monoubiquitinated PCNA. We discuss the physiological relevance of the different modes of the polyubiquitination to the choice of cells between TLS and TS under different conditions.
Indexed as
Identifiers
What OpenQuestion holds
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.