ArticleProceedings of the National Academy of Sciences of the United States of America2008
Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Repertoire Sequencing of B Cells Elucidates the Role of UNG and Mismatch Repair Proteins in Somatic Hypermutation in Humans.Frontiers in immunology · 2019Pooled it
- UNG-RPA interaction governs the choice between high-fidelity and mutagenic uracil repair.Nucleic acids research · 2026Article
- PCNA Macromolecular Complexes: PCNA Serves as a Molecular Hub Regulating Multiple Cellular Processes Inside and Outside of the Nucleus.Advances in experimental medicine and biology · 2026Review
- Review
- Primordial germ cell DNA demethylation and development require DNA translesion synthesis.Nature communications · 2024Article
- The deubiquitinase cofactor UAF1 interacts with USP1 and plays an essential role in spermiogenesis.iScience · 2024Article
- Role of Rad18 in B cell activation and lymphomagenesis.Scientific reports · 2024Article
- Transgenerational epigenetic effects imposed by neonicotinoid thiacloprid exposure.Life science alliance · 2024Article
- Comparative analysis of the immune responses of CcIgZ3 in mucosal tissues and the co-expression of CcIgZ3 and PCNA in the gills of common carp (Cyprinus carpio L.) in response to TNP-LPS.BMC veterinary research · 2024Article
- Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine.International journal of molecular sciences · 2023Review
- Unraveling DNA Repair Processes In Vivo: Insights from Zebrafish Studies.International journal of molecular sciences · 2023Review
- A FRET-Based Assay for the Identification of PCNA Inhibitors.International journal of molecular sciences · 2023Article
- Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in Exo1D173A mice.Nucleic acids research · 2022Article
- AID function in somatic hypermutation and class switch recombination.Acta biochimica et biophysica Sinica · 2022Review
- The Functions of PCNA in Tumor Stemness and Invasion.International journal of molecular sciences · 2022Article
- Expression of Constitutive Fusion of Ubiquitin to PCNA Restores the Level of Immunoglobulin A/T Mutations During Somatic Hypermutation in the Ramos Cell Line.Frontiers in immunology · 2022Article
- Review
- Cyclin N-Terminal Domain-Containing-1 Coordinates Meiotic Crossover Formation with Cell-Cycle Progression in a Cyclin-Independent Manner.Cell reports · 2020Article
- A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis.Frontiers in cell and developmental biology · 2020Review
- Siva plays a critical role in mouse embryonic development.Cell death and differentiation · 2020Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes are dependent upon activation-induced cytidine deaminase (AID)-induced mutations. The scaffolding properties of proliferating cell nuclear antigen (PCNA) and ubiquitylation of its residue K164 have been suggested to play an important role organizing the error-prone repair events that contribute to the AID-induced diversification of the Ig locus. We generated knockout mice for PCNA (Pcna(-/-)), which were embryonic lethal. Expression of PCNA with the K164R mutation rescued the lethal phenotype, but the mice (Pcna(-/-)tg(K164R)) displayed a meiotic defect in early pachynema and were sterile. B cells proliferated normally in Pcna(-/-)tg(K164R) mice, but a PCNA-K164R mutation resulted in impaired ex vivo CSR to IgG1 and IgG3, which was associated with reduced mutation frequency at the switch regions and a bias toward blunt junctions. Analysis of the heavy chain V186.2 region after NP-immunization showed in Pcna(-/-)tg(K164R) mice a significant reduction in the mutation frequency of A:T residues in WA motifs preferred by polymerase-eta (Poleta), and a strand-biased increase in the mutation frequency of G residues, preferentially in the context of AID-targeted GYW motifs. The phenotype of Pcna(-/-)tg(K164R) mice supports the idea that ubiquitylation of PCNA participates directly in the meiotic process and the diversification of the Ig locus through class-switch recombination (CSR) and somatic hypermutation (SHM).
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.