ArticleNucleic acids research2023
Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 16 citations in OpenAlex.
- Molecular and structural basis for replication initiation and strand separation by human mitochondrial DNA polymerase γ.Nucleic acids research · 2026Article
- Structural and single-molecule insights into the core human mitochondrial DNA replisome.The Biochemical journal · 2026Review
- Pol γ possesses separate metal binding sites for polymerase and strand displacement functions.Nucleic acids research · 2026Article
- Regulation of Pfh1 helicase activity by nucleic acid interactions and mitochondrial SSB.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dissecting the role of PCNA and Pif1 in replication of individual DNA molecules by DNA polymerase δ.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial DNA in systemic lupus erythematosus: pathogenic mechanisms, clinical biomarkers, and precision therapeutic strategies.Frontiers in immunology · 2026Review
- Autoregulation of the real-time kinetics of the human mitochondrial replicative helicase.Nature communications · 2025Article
- Mechanistic insights into direct DNA and RNA strand transfer and dynamic protein exchange of SSB and RPA.Nucleic acids research · 2025Article
- An alternative model for maternal mtDNA inheritance.Nature genetics · 2025Article
- Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps.Nucleic acids research · 2025Article
- Structures of the mitochondrial single-stranded DNA binding protein with DNA and DNA polymerase γ.Nucleic acids research · 2024Article
- The mutation R107Q alters mtSSB ssDNA compaction ability and binding dynamics.Nucleic acids research · 2024Article
- Single-molecule imaging of genome maintenance proteins encountering specific DNA sequences and structures.DNA repair · 2023Review
- Unravelling How Single-Stranded DNA Binding Protein Coordinates DNA Metabolism Using Single-Molecule Approaches.International journal of molecular sciences · 2023Review
- Bst polymerase - a humble relative of Taq polymerase.Computational and structural biotechnology journal · 2023Review
- Editorial: Energy-producing organelles and the nucleus: a phenomenal genomic friendship.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Many replicative DNA polymerases couple DNA replication and unwinding activities to perform strand displacement DNA synthesis, a critical ability for DNA metabolism. Strand displacement is tightly regulated by partner proteins, such as single-stranded DNA (ssDNA) binding proteins (SSBs) by a poorly understood mechanism. Here, we use single-molecule optical tweezers and biochemical assays to elucidate the molecular mechanism of strand displacement DNA synthesis by the human mitochondrial DNA polymerase, Polγ, and its modulation by cognate and noncognate SSBs. We show that Polγ exhibits a robust DNA unwinding mechanism, which entails lowering the energy barrier for unwinding of the first base pair of the DNA fork junction, by ∼55%. However, the polymerase cannot prevent the reannealing of the parental strands efficiently, which limits by ∼30-fold its strand displacement activity. We demonstrate that SSBs stimulate the Polγ strand displacement activity through several mechanisms. SSB binding energy to ssDNA additionally increases the destabilization energy at the DNA junction, by ∼25%. Furthermore, SSB interactions with the displaced ssDNA reduce the DNA fork reannealing pressure on Polγ, in turn promoting the productive polymerization state by ∼3-fold. These stimulatory effects are enhanced by species-specific functional interactions and have significant implications in the replication of the human mitochondrial DNA.
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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.