ReviewNucleic acids research2011
Clustering of Alpers disease mutations and catalytic defects in biochemical variants reveal new features of molecular mechanism of the human mitochondrial replicase, Pol γ.
Review in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Progressive cognitive impairment and ventricular tachycardia in a boy with biallelic POLG variants and a de novo RYR2 variation.Scientific reports · 2026Article
- Treatment of Autism Spectrum Disorders by Mitochondrial-targeted Drug: Future of Neurological Diseases Therapeutics.Current neuropharmacology · 2023Review
- Mitochondrial DNA maintenance in Drosophila melanogaster.Bioscience reports · 2022Review
- Remdesivir triphosphate blocks DNA synthesis and increases exonucleolysis by the replicative mitochondrial DNA polymerase, Pol γ.Mitochondrion · 2021Article
- Novel biallelic mutations in POLG gene: large deletion and missense variant associated with PEO.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Article
- A perspective on human cell models for POLG-spectrum disorders: advantages and disadvantages of CRISPR-Cas-based vs. patient-derived iPSC models.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2021Article
- fcScan: a versatile tool to cluster combinations of sites using genomic coordinates.BMC bioinformatics · 2020Article
- POLG-related disorders and their neurological manifestations.Nature reviews. Neurology · 2019Review
- Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase.Scientific reports · 2018Article
- Pathogenicity in POLG syndromes: DNA polymerase gamma pathogenicity prediction server and database.BBA clinical · 2017Article
- Human mitochondrial DNA replication machinery and disease.Current opinion in genetics & development · 2016Review
- A Clinical, Neuropathological and Genetic Study of Homozygous A467T POLG-Related Mitochondrial Disease.PloS one · 2016Article
- Alpers-Huttenlocher syndrome: the role of a multidisciplinary health care team.Journal of multidisciplinary healthcare · 2016Review
- Structure, function and evolution of the animal mitochondrial replicative DNA helicase.Critical reviews in biochemistry and molecular biology · 2016Review
- Mitochondrial Single-stranded DNA-binding Proteins Stimulate the Activity of DNA Polymerase γ by Organization of the Template DNA.The Journal of biological chemistry · 2015Article
- Yeast model analysis of novel polymerase gamma variants found in patients with autosomal recessive mitochondrial disease.Human genetics · 2015Article
- Evolution of the metazoan mitochondrial replicase.Genome biology and evolution · 2015Article
- Alpers disease mutations in human DNA polymerase gamma cause catalytic defects in mitochondrial DNA replication by distinct mechanisms.Frontiers in genetics · 2015Article
- DNA polymerase γ and disease: what we have learned from yeast.Frontiers in genetics · 2015Review
- Polymorphisms in DNA polymerase γ affect the mtDNA stability and the NRTI-induced mitochondrial toxicity in Saccharomyces cerevisiae.Mitochondrion · 2015Article
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5 authors.
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Abstract
Mutations in Pol γ represent a major cause of human mitochondrial diseases, especially those affecting the nervous system in adults and in children. Recessive mutations in Pol γ represent nearly half of those reported to date, and they are nearly uniformly distributed along the length of the POLG1 gene (Human DNA Polymerase gamma Mutation Database); the majority of them are linked to the most severe form of POLG syndrome, Alpers-Huttenlocher syndrome. In this report, we assess the structure-function relationships for recessive disease mutations by reviewing existing biochemical data on site-directed mutagenesis of the human, Drosophila and yeast Pol γs, and their homologs from the family A DNA polymerase group. We do so in the context of a molecular model of Pol γ in complex with primer-template DNA, which we have developed based upon the recently solved crystal structure of the apoenzyme form. We present evidence that recessive mutations cluster within five distinct functional modules in the catalytic core of Pol γ. Our results suggest that cluster prediction can be used as a diagnosis-supporting tool to evaluate the pathogenic role of new Pol γ variants.
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