ArticleAmerican journal of human genetics2006
Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia.
Article in American journal of human genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 245 citations in OpenAlex.
- Accumulated mtDNA mutations are linked to specific impairments in NADH-linked respiration.iScience · 2026Article
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Coordinated DNA polymerization by Polγ and the region of LonP1 regulated proteolysis.Nucleic acids research · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- POLG2-Linked Mitochondrial Disease: Functional Insights from New Mutation Carriers and Review of the Literature.Cerebellum (London, England) · 2024Review
- Decoding mitochondrial DNA damage and repair associated withFrontiers in cellular and infection microbiology · 2024Review
- Interference with mitochondrial metabolism could serve as a potential therapeutic strategy for advanced prostate cancer.PloS one · 2024Article
- Structure-specific roles for PolG2-DNA complexes in maintenance and replication of mitochondrial DNA.Nucleic acids research · 2023Article
- Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability.EMBO molecular medicine · 2023Article
- Nuclear genetic control of mtDNA copy number and heteroplasmy in humans.medRxiv : the preprint server for health sciences · 2023Article
- Progressive external ophthalmoplegia.Handbook of clinical neurology · 2023Review
- Article
- Detection of repeat expansions in large next generation DNA and RNA sequencing data without alignment.Scientific reports · 2022Article
- Novel and recurrent nuclear gene variations in a cohort of Chinese progressive external ophthalmoplegia patients with multiple mtDNA deletions.Molecular genetics & genomic medicine · 2022Article
- Mice lacking the mitochondrial exonuclease MGME1 develop inflammatory kidney disease with glomerular dysfunction.PLoS genetics · 2022Article
- Comparative Genomics Provides Insights into Adaptive Evolution in Tactile-Foraging Birds.Genes · 2022Article
- Mitochondrial Neurodegeneration.Cells · 2022Review
- Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies.Journal of neuromuscular diseases · 2022Review
- Case Report: Thymidine Kinase 2 (TK2) Deficiency: A Novel Mutation Associated With Childhood-Onset Mitochondrial Myopathy and Atypical Progression.Frontiers in neurology · 2022Article
50 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
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Abstract
DNA polymerase gamma (pol gamma ) is required to maintain the genetic integrity of the 16,569-bp human mitochondrial genome (mtDNA). Mutation of the nuclear gene for the catalytic subunit of pol gamma (POLG) has been linked to a wide range of mitochondrial diseases involving mutation, deletion, and depletion of mtDNA. We describe a heterozygous dominant mutation (c.1352G-->A/p.G451E) in POLG2, the gene encoding the p55 accessory subunit of pol gamma , that causes progressive external ophthalmoplegia with multiple mtDNA deletions and cytochrome c oxidase (COX)-deficient muscle fibers. Biochemical characterization of purified, recombinant G451E-substituted p55 protein in vitro revealed incomplete stimulation of the catalytic subunit due to compromised subunit interaction. Although G451E p55 retains a wild-type ability to bind DNA, it fails to enhance the DNA-binding strength of the p140-p55 complex. In vivo, the disease most likely arises through haplotype insufficiency or heterodimerization of the mutated and wild-type proteins, which promote mtDNA deletions by stalling the DNA replication fork. The progressive accumulation of mtDNA deletions causes COX deficiency in muscle fibers and results in the clinical phenotype.
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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.