ArticleBiochemistry2010
The p12 subunit of human polymerase delta modulates the rate and fidelity of DNA synthesis.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- Interpreting the effects of DNA polymerase variants at the structural level.Molecular oncology · 2026Article
- Review
- In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease.Nature genetics · 2025Article
- Profiling Proteins and Phosphorylation Sites During T Cell Activation Using an Integrated Thermal Shift Assay.Molecular & cellular proteomics : MCP · 2024Article
- Replication of [AT/TA]Biochemistry · 2024Article
- Replication of [AT/TA]bioRxiv : the preprint server for biology · 2023Article
- High-Throughput Exonuclease Assay Based on the Fluorescent Base Analogue 2-Aminopurine.ACS omega · 2023Article
- Structural and Molecular Kinetic Features of Activities of DNA Polymerases.International journal of molecular sciences · 2022Review
- Beyond the Lesion: Back to High Fidelity DNA Synthesis.Frontiers in molecular biosciences · 2021Review
- Elevated DNA Polymerase Delta 1 Expression Correlates With Tumor Progression and Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Kinetic investigation of the polymerase and exonuclease activities of human DNA polymerase ε holoenzyme.The Journal of biological chemistry · 2020Article
- Quaternary structural diversity in eukaryotic DNA polymerases: monomeric to multimeric form.Current genetics · 2020Review
- Structure of the processive human Pol δ holoenzyme.Nature communications · 2020Article
- Dynamic Assembly and Disassembly of the Human DNA Polymerase δ Holoenzyme on the Genome In Vivo.Cell reports · 2020Article
- Human DNA polymerase delta is a pentameric holoenzyme with a dimeric p12 subunit.Life science alliance · 2019Article
- The p12 subunit of human polymerase δ uses an atypical PIP box for molecular recognition of proliferating cell nuclear antigen (PCNA).The Journal of biological chemistry · 2019Article
- Discovery of a novel DNA polymerase inhibitor and characterization of its antiproliferative properties.Cancer biology & therapy · 2019Article
- Loss of the p12 subunit of DNA polymerase delta leads to a defect in HR and sensitization to PARP inhibitors.DNA repair · 2019Article
- p15PAF binding to PCNA modulates the DNA sliding surface.Nucleic acids research · 2018Article
- Plant organellar DNA polymerases are replicative and translesion DNA synthesis polymerases.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
This study examines the role of the p12 subunit in the function of the human DNA polymerase delta (Pol delta) holoenzyme by comparing the kinetics of DNA synthesis and degradation catalyzed by the four-subunit complex, the three-subunit complex lacking p12, and site-directed mutants of each lacking proofreading exonuclease activity. Results show that p12 modulates the rate and fidelity of DNA synthesis by Pol delta. All four complexes synthesize DNA in a rapid burst phase and a slower, more linear phase. In the presence of p12, the burst rates of DNA synthesis are approximately 5 times faster, while the affinity of the enzyme for its DNA and dNTP substrates appears unchanged. The p12 subunit alters Pol delta fidelity by modulating the proofreading 3' to 5' exonuclease activity. In the absence of p12, Pol delta is more likely to proofread DNA synthesis because it cleaves single-stranded DNA twice as fast and transfers mismatched DNA from the polymerase to the exonuclease sites 9 times faster. Pol delta also extends mismatched primers 3 times more slowly in the absence of p12. Taken together, the changes that p12 exerts on Pol delta are ones that can modulate its fidelity of DNA synthesis. The loss of p12, which occurs in cells upon exposure to DNA-damaging agents, converts Pol delta to a form that has an increased capacity for proofreading.
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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.