ArticleProceedings of the National Academy of Sciences of the United States of America2010
Drosophila topo IIIalpha is required for the maintenance of mitochondrial genome and male germ-line stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Topoisomerase 3b facilitates piRNA biogenesis to promote transposon silencing and germ cell development.Cell reports · 2025Article
- A mitochondrial redox switch licenses the onset of morphogenesis in animals.bioRxiv : the preprint server for biology · 2024Article
- Mitochondrial Differentiation during Spermatogenesis: Lessons fromInternational journal of molecular sciences · 2024Review
- Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life.Cells · 2024Review
- TOP3A coupling with replication forks and repair of TOP3A cleavage complexes.Cell cycle (Georgetown, Tex.) · 2024Review
- Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability.EMBO molecular medicine · 2023Article
- Two type I topoisomerases maintain DNA topology in human mitochondria.Nucleic acids research · 2022Article
- Top3α is the replicative topoisomerase in mitochondrial DNA replication.Nucleic acids research · 2022Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- DNA topoisomerases: Advances in understanding of cellular roles and multi-protein complexes via structure-function analysis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2021Review
- Mitochondrial Control of Stem Cell State and Fate: Lessons FromFrontiers in cell and developmental biology · 2021Review
- The many lives of type IA topoisomerases.The Journal of biological chemistry · 2020Review
- Advanced Parental Age at Conception and Sex Affects Mitochondrial DNA Copy Number in Human and Fruit Flies.The journals of gerontology. Series A, Biological sciences and medical sciences · 2019Article
- Sex and age specific reduction in stress resistance and mitochondrial DNA copy number in Drosophila melanogaster.Scientific reports · 2019Article
- Twist and Turn-Topoisomerase Functions in Mitochondrial DNA Maintenance.International journal of molecular sciences · 2019Review
- Topoisomerases as anticancer targets.The Biochemical journal · 2018Review
- Topoisomerase 3α Is Required for Decatenation and Segregation of Human mtDNA.Molecular cell · 2018Article
- Electron tomographic analysis reveals ultrastructural features of mitochondrial cristae architecture which reflect energetic state and aging.Scientific reports · 2017Article
- Physiological Roles of DNA Double-Strand Breaks.Journal of nucleic acids · 2017Review
- Roles of eukaryotic topoisomerases in transcription, replication and genomic stability.Nature reviews. Molecular cell biology · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Topoisomerase IIIalpha (topo IIIalpha), a member of the conserved Type IA subfamily of topoisomerases, is required for the cell proliferation in mitotic tissues, but has a lesser effect on DNA endoreplication. The top3alpha gene encodes two forms of protein by utilizing alternative translation initiation sites: one (short form) with the nuclear localization signal only, exclusively localized in the nuclei, and the other (long form), retaining a mitochondrial import sequence at the N-terminus and the nuclear localization sequence at the C-terminus, localized primarily in the mitochondria, though with a small portion in the nuclei. Both forms of topo IIIalpha can rescue the viability of null mutants of top3alpha. No apparent defect is associated with the flies rescued by the long form; short-form-rescued flies (referred to as M1L), however, exhibit defects in fertilities. M1L females are sterile. They can lay eggs but with mitochondrial DNA (mtDNA) copy number and ATP content decreased by 20- and 2- to 3-fold, respectively, and they fail to hatch. Of the newly eclosed M1L males, 33% are completely sterile, whereas the rest have residual fertilities that are quickly lost in 6 days. The fertility loss of M1L males is caused by the disruption of the individualization complex and a progressive loss of germ-line stem cells. This study implicates topo IIIalpha in the maintenance of mtDNA and male germ-line stem cells, and thus is a causative candidate for genetic disorders associated with mtDNA depletion.
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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 Socratic graph.