ArticleProceedings of the National Academy of Sciences of the United States of America2002
The accessory subunit of DNA polymerase gamma is essential for mitochondrial DNA maintenance and development in Drosophila melanogaster.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Article
- Our current understanding of the biological impact of endometrial cancer mtDNA genome mutations and their potential use as a biomarker.Frontiers in oncology · 2024Review
- Reclassification of family A DNA polymerases reveals novel functional subfamilies and distinctive structural features.Nucleic acids research · 2023Article
- Mitochondrial DNA maintenance in Drosophila melanogaster.Bioscience reports · 2022Review
- Mapping Adverse Outcome Pathways for Kidney Injury as a Basis for the Development of Mechanism-Based Animal-Sparing Approaches to Assessment of Nephrotoxicity.Frontiers in toxicology · 2022Article
- Article
- Large-scale RNAi screen identified Dhpr as a regulator of mitochondrial morphology and tissue homeostasis.Science advances · 2019Article
- Characterization of the human homozygous R182W POLG2 mutation in mitochondrial DNA depletion syndrome.PloS one · 2018Article
- Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance.Frontiers in molecular biosciences · 2017Review
- Mitochondrial retrograde signaling regulates neuronal function.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- POLG2 disease variants: analyses reveal a dominant negative heterodimer, altered mitochondrial localization and impaired respiratory capacity.Human molecular genetics · 2015Article
- Evolution of the metazoan mitochondrial replicase.Genome biology and evolution · 2015Article
- Screen for mitochondrial DNA copy number maintenance genes reveals essential role for ATP synthase.Molecular systems biology · 2014Article
- Polg2 is essential for mammalian embryogenesis and is required for mtDNA maintenance.Human molecular genetics · 2013Article
- A cytoplasmic suppressor of a nuclear mutation affecting mitochondrial functions in Drosophila.Genetics · 2012Article
- Biochemical analysis of human POLG2 variants associated with mitochondrial disease.Human molecular genetics · 2011Article
- Animal models of mitochondrial DNA transactions in disease and ageing.Experimental gerontology · 2010Review
- Bacteria, yeast, worms, and flies: exploiting simple model organisms to investigate human mitochondrial diseases.Developmental disabilities research reviews · 2010Review
- Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo.PloS one · 2009Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
DNA polymerase gamma, Pol gamma, is the key replicative enzyme in animal mitochondria. The Drosophila enzyme is a heterodimer comprising catalytic and accessory subunits of 125 kDa and 35 kDa, respectively. Both subunits have been cloned and characterized in a variety of model systems, and genetic mutants of the catalytic subunit were first identified in Drosophila, as chemically induced mutations that disrupt larval behavior (tamas). Mutations in the gene encoding the accessory subunit have not yet been described in any organism. Here, we report the consequences of null mutations upon mitochondrial DNA (mtDNA) replication and morphology, cell proliferation, and organismal viability. Mutations in the accessory subunit cause lethality during early pupation, concomitant with loss of mtDNA and mitochondrial mass, and reduced cell proliferation in the central nervous system. Surprisingly, the function of the central nervous system and muscle, as assessed in a locomotion assay, are only marginally affected. This finding is in contrast to our previous findings that disruption in the function of the catalytic subunit causes severe reduction in larval locomotion. We discuss our results in the context of current hypotheses for the function of the accessory subunit in mtDNA replication.
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