Document Type
Article
Publication Date
3-11-2025
Abstract
Members of the Pol A family of DNA polymerases, found across all domains of life, utilize various strategies for DNA strand separation during replication. In higher eukaryotes, mitochondrial DNA polymerase γ relies on the replicative helicase TWINKLE, whereas the yeast ortholog, Mip1, can unwind DNA independently. Using Mip1 as a model, we present a series of high-resolution cryo-EM structures that capture the process of DNA strand displacement. Our data reveal previously unidentified structural elements that facilitate the unwinding of the downstream DNA duplex. Yeast cells harboring Mip1 variants defective in strand displacement exhibit impaired oxidative phosphorylation and loss of mtDNA, corroborating the structural observations. This study provides a molecular basis for the intrinsic strand displacement activity of Mip1 and illuminates the distinct unwinding mechanisms utilized by Pol A family DNA polymerases.
Recommended Citation
Nayak, Ashok; Sokolova, Viktoriia; Sillamaa, Sirelin; Herbine, Karl; Sedman, Juhan; and Temiakov, Dmitry, "Structural Basis for Intrinsic Strand Displacement Activity of Mitochondrial DNA Polymerase" (2025). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 277.
https://jdc.jefferson.edu/bmpfp/277
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
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PubMed ID
40069189
Language
English
Included in
Biochemistry Commons, Cell Anatomy Commons, Medicine and Health Sciences Commons, Molecular Biology Commons
Comments
This article is the author's final published version in Nature Communications, Volume 16, Issue 1, 2025, Article number 2417.
The published version is available at https://doi.org/10.1038/s41467-025-57594-z.
Copyright © The Author(s) 2025