ArticleNucleic acids research2022
Human DNA polymerase α has a strong mutagenic potential at the initial steps of DNA synthesis.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- The human primosome requires replication protein A when copying DNA with inverted repeats.Nucleic acids research · 2025Article
- New Progress on DNA Primase Subunit Enzymes Research and Link to Cancer Development and Treatment Approaches.Current cancer drug targets · 2025Review
- Strategies and procedures to generate chimeric DNA polymerases for improved applications.Applied microbiology and biotechnology · 2024Review
- Identification of a novel family B DNA polymerase from Enterococcus phage IME199 and its overproduction in Escherichia coli BL21(DE3).Microbial cell factories · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
DNA polymerase α (Polα) is essential for DNA replication initiation and makes a notable contribution to genome mutagenesis. The activity and fidelity of Polα during the early steps of DNA replication have not been well studied. Here we show that at the beginning of DNA synthesis, when extending the RNA primer received from primase, Polα is more mutagenic than during the later DNA elongation steps. Kinetic and binding studies revealed substantially higher activity and affinity to the template:primer when Polα interacts with ribonucleotides of a chimeric RNA-DNA primer. Polα activity greatly varies during first six steps of DNA synthesis, and the bias in the rates of correct and incorrect dNTP incorporation leads to impaired fidelity, especially upon the second step of RNA primer extension. Furthermore, increased activity and stability of Polα/template:primer complexes containing RNA-DNA primers result in higher efficiency of mismatch extension.
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