Cited by 415Mitochondrial Function and PathologyDNA Repair MechanismsDNA and Nucleic Acid Chemistry

DNA Polymerase γ, The Mitochondrial Replicase

Kaguni, Laurie S.·2004·Annual Review of Biochemistry

Abstract

DNA polymerase (pol) gamma is the sole DNA polymerase in animal mitochondria. Biochemical and genetic evidence document a key role for pol gamma in mitochondrial DNA replication, and whereas DNA repair and recombination were thought to be limited or absent in animal mitochondria, both have been demonstrated in recent years. Thus, the mitochondrial replicase is also apparently responsible for the relevant DNA synthetic reactions in these processes. Pol gamma comprises a catalytic core in a heterodimeric complex with an accessory subunit. The two-subunit holoenzyme is an efficient and processive polymerase, which exhibits high fidelity in nucleotide selection and incorporation while proofreading errors with its intrinsic 3' 5' exonuclease. Incorporation of nucleotide analogs followed by proofreading failure leads to mitochondrial toxicity in antiviral therapy, and misincorporation during DNA replication leads to mitochondrial mutagenesis and dysfunction. This review describes our current understanding of pol gamma biochemistry and biology, and it introduces other key proteins that function at the mitochondrial DNA replication fork.

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Crossref · 10.1146/annurev.biochem.72.121801.161455

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Authors
Kaguni, L. S.
Affiliations
Michigan State University (US)
Corresponding author
Kaguni, Laurie S.
Venue
Annual Review of Biochemistry
Published
2004-06
Volume
73
Issue
1
Pages
293-320
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
OpenAlex
W2128968369
Cited by
414
References
156
Citations by year
2026: 8 · 2025: 13 · 2024: 11 · 2023: 12 · 2022: 13 · 2021: 12 · 2020: 15 · 2019: 10 · 2018: 11 · 2017: 16 · 2016: 23 · 2015: 16 · 2014: 16 · 2013: 21 · 2012: 26
FWCI
1.40
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Cancer Society
  • National Institutes of Health (5r01hl059656-03, 5r01gm034042-03)
  • National Heart, Lung, and Blood Institute (HL59656)
  • National Institute of General Medical Sciences (R01GM045295, GM34042, GM45295)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
DNA polymerase gamma, mitochondrial DNA replication, mitochondrial DNA repair, DNA recombination, nucleotide misincorporation, mitochondrial mutagenesis, mitochondrial dysfunction
MeSH terms
DNA Polymerase gamma, Amino Acid Sequence, Animals, DNA-Directed DNA Polymerase, DNA Replication, Exonucleases, Humans, Mitochondria, Models, Molecular, Molecular Sequence Data, Mutagenesis, Sequence Homology, Amino Acid, Protein Subunits, History, 20th Century

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