ArticleDNA repair2017
DNA polymerases eta and kappa exchange with the polymerase delta holoenzyme to complete common fragile site synthesis.
Article in DNA repair, 2017. 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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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.
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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.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Human cytomegalovirus regulates host DNA repair machinery for viral genome integrity.Nucleic acids research · 2026Article
- Overcoming natural replication barriers formed by DNA structures and the role of repositioning to the nuclear periphery.DNA repair · 2025Review
- Article
- DNA polymerase zeta can efficiently replicate structures formed by AT/TA repeat sequences and prevent their deletion.Nucleic acids research · 2025Article
- Complex roles for proliferating cell nuclear antigen in restricting human cytomegalovirus replication.bioRxiv : the preprint server for biology · 2025Article
- Review
- Activity of DNA polymerase κ across the genome in human fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Microsatellite break-induced replication generates highly mutagenized extrachromosomal circular DNAs.NAR cancer · 2024Article
- Insights into common fragile site instability: DNA replication challenges at DNA repeat sequences.Emerging topics in life sciences · 2023Article
- Review
- Global landscape of replicative DNA polymerase usage in the human genome.Nature communications · 2022Article
- Variation in G-quadruplex sequence and topology differentially impacts human DNA polymerase fidelity.DNA repair · 2022Article
- Translesion polymerase eta both facilitates DNA replication and promotes increased human genetic variation at common fragile sites.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A Catalytically Independent Function of Human DNA Polymerase Kappa Controls the Stability and Abundance of Checkpoint Kinase 1.Molecular and cellular biology · 2021Article
- Cryo-EM structure of human Pol κ bound to DNA and mono-ubiquitylated PCNA.Nature communications · 2021Article
- Expression of the cancer-associated DNA polymerase ε P286R in fission yeast leads to translesion synthesis polymerase dependent hypermutation and defective DNA replication.PLoS genetics · 2021Article
- Mind the replication gap.Royal Society open science · 2021Review
- Non-B DNA: a major contributor to small- and large-scale variation in nucleotide substitution frequencies across the genome.Nucleic acids research · 2021Article
- Article
- Replication stress at microsatellites causes DNA double-strand breaks and break-induced replication.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Common fragile sites (CFSs) are inherently unstable genomic loci that are recurrently altered in human tumor cells. Despite their instability, CFS are ubiquitous throughout the human genome and associated with large tumor suppressor genes or oncogenes. CFSs are enriched with repetitive DNA sequences, one feature postulated to explain why these loci are inherently difficult to replicate, and sensitive to replication stress. We have shown that specialized DNA polymerases (Pols) η and κ replicate CFS-derived sequences more efficiently than the replicative Pol δ. However, we lacked an understanding of how these enzymes cooperate to ensure efficient CFS replication. Here, we designed a model of lagging strand replication with RFC loaded PCNA that allows for maximal activity of the four-subunit human Pol δ holoenzyme, Pol η, and Pol κ in polymerase mixing assays. We discovered that Pol η and κ are both able to exchange with Pol δ stalled at repetitive CFS sequences, enhancing Normalized Replication Efficiency. We used this model to test the impact of PCNA mono-ubiquitination on polymerase exchange, and found no change in polymerase cooperativity in CFS replication compared with unmodified PCNA. Finally, we modeled replication stress in vitro using aphidicolin and found that Pol δ holoenzyme synthesis was significantly inhibited in a dose-dependent manner, preventing any replication past the CFS. Importantly, Pol η and κ were still proficient in rescuing this stalled Pol δ synthesis, which may explain, in part, the CFS instability phenotype of aphidicolin-treated Pol η and Pol κ-deficient cells. In total, our data support a model wherein Pol δ stalling at CFSs allows for free exchange with a specialized polymerase that is not driven by PCNA.
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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.