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Structure paper

TitleStructural basis for intrinsic strand displacement activity of mitochondrial DNA polymerase.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 2417, Year 2025
Publish dateMar 11, 2025
AuthorsAshok R Nayak / Viktoriia Sokolova / Sirelin Sillamaa / Karl Herbine / Juhan Sedman / Dmitry Temiakov /
PubMed AbstractMembers 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 ...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.
External linksNat Commun / PubMed:40069189 / PubMed Central
MethodsEM (single particle)
Resolution2.42 - 2.96 Å
Structure data

45194

9c51

EMDB-45194, PDB-9c51:
Cryo-EM structure of the Strand displacement Complex (IV) of Yeast Mitochondrial DNA polymerase Gamma (MIP1) with downstream DNA
Method: EM (single particle) / Resolution: 2.42 Å

45195

9c52

EMDB-45195, PDB-9c52:
Cryo-EM structure of the Strand displacement Complex (I) of Yeast Mitochondrial DNA polymerase Gamma (MIP1) with downstream DNA
Method: EM (single particle) / Resolution: 2.64 Å

45196

9c53

EMDB-45196: Cryo-EM structure of the Strand displacement Complex (III) of Yeast Mitochondrial DNA polymerase Gamma (MIP1) with downstream DNA
PDB-9c53: Cryo-EM structure of the Strand displacement Complex (II) of Yeast Mitochondrial DNA polymerase Gamma (MIP1) with downstream DNA
Method: EM (single particle) / Resolution: 2.6 Å

46497

9d2i

EMDB-46497, PDB-9d2i:
Cryo-EM structure of the Strand displacement Complex (III) of Yeast Mitochondrial DNA polymerase Gamma (MIP1) with downstream DNA
Method: EM (single particle) / Resolution: 2.96 Å

Chemicals

ChemComp-DTP:
2'-DEOXYADENOSINE 5'-TRIPHOSPHATE

ChemComp-MG:
Unknown entry

ChemComp-2DT:
3'-DEOXYTHYMIDINE-5'-MONOPHOSPHATE

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • synthetic construct (others)
KeywordsTransferase/DNA / Mitochondrial DNA Polymerase Gamma / Strand displacement complex / MIP1 / REPLICATION / Helicase independent DNA polymerase / Transferase-DNA complex

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