ArticleNucleic acids research2019
Effective mismatch repair depends on timely control of PCNA retention on DNA by the Elg1 complex.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma.International journal of molecular sciences · 2026Review
- Immune checkpoint inhibitors in dMMR-MSI-H colorectal cancer: rationale, progress and prospects.Frontiers in immunology · 2026Review
- Comprehensive whole-genome sequencing reveals origins of mutational signatures associated with aging, mismatch repair deficiency and temozolomide chemotherapy.Nucleic acids research · 2025Article
- Dual role of proliferating cell nuclear antigen monoubiquitination in facilitating Fanconi anemia-mediated interstrand crosslink repair.PNAS nexus · 2024Article
- Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review.BMC medical genomics · 2024Article
- The Atad5 RFC-like complex is the major unloader of proliferating cell nuclear antigen in Xenopus egg extracts.The Journal of biological chemistry · 2024Article
- Elevated MSH2 MSH3 expression interferes with DNA metabolism in vivo.Nucleic acids research · 2023Article
- Effects of Defective Unloading and Recycling of PCNA Revealed by the Analysis ofInternational journal of molecular sciences · 2023Article
- Article
- Unraveling the Molecular Impact of Sperm DNA Damage on Human Reproduction.Advances in experimental medicine and biology · 2022Article
- Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair.Nucleic acids research · 2021Article
- Strand discrimination in DNA mismatch repair.DNA repair · 2021Review
- A study of deregulated MMR pathways and anticancer potential of curcuma derivatives using computational approach.Scientific reports · 2021Article
- Prevention of Skin Carcinogenesis by the Non-β-blocking R-carvedilol Enantiomer.Cancer prevention research (Philadelphia, Pa.) · 2021Article
- DNA Mismatch Repair and its Role in Huntington's Disease.Journal of Huntington's disease · 2021Review
- Eukaryotic clamp loaders and unloaders in the maintenance of genome stability.Experimental & molecular medicine · 2020Review
- Structure of the human clamp loader reveals an autoinhibited conformation of a substrate-bound AAA+ switch.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Proliferating cell nuclear antigen (PCNA) is a sliding clamp that acts as a central co-ordinator for mismatch repair (MMR) as well as DNA replication. Loss of Elg1, the major subunit of the PCNA unloader complex, causes over-accumulation of PCNA on DNA and also increases mutation rate, but it has been unclear if the two effects are linked. Here we show that timely removal of PCNA from DNA by the Elg1 complex is important to prevent mutations. Although premature unloading of PCNA generally increases mutation rate, the mutator phenotype of elg1Δ is attenuated by PCNA mutants PCNA-R14E and PCNA-D150E that spontaneously fall off DNA. In contrast, the elg1Δ mutator phenotype is exacerbated by PCNA mutants that accumulate on DNA due to enhanced electrostatic PCNA-DNA interactions. Epistasis analysis suggests that PCNA over-accumulation on DNA interferes with both MMR and MMR-independent process(es). In elg1Δ, over-retained PCNA hyper-recruits the Msh2-Msh6 mismatch recognition complex through its PCNA-interacting peptide motif, causing accumulation of MMR intermediates. Our results suggest that PCNA retention controlled by the Elg1 complex is critical for efficient MMR: PCNA needs to be on DNA long enough to enable MMR, but if it is retained too long it interferes with downstream repair steps.
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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.