ArticleThe Journal of biological chemistry2010
Disease variants of the human mitochondrial DNA helicase encoded by C10orf2 differentially alter protein stability, nucleotide hydrolysis, and helicase activity.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 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
- Single-molecule fluorescence reveals the DNA unwinding mechanism of mitochondrial helicase TWINKLE and its interplay with single-stranded DNA-binding proteins.Nucleic acids research · 2025Article
- Autoregulation of the real-time kinetics of the human mitochondrial replicative helicase.Nature communications · 2025Article
- Single-molecule imaging of genome maintenance proteins encountering specific DNA sequences and structures.DNA repair · 2023Review
- Method for the structural analysis of Twinkle mitochondrial DNA helicase by cryo-EM.Methods (San Diego, Calif.) · 2022Article
- Structural insight and characterization of human Twinkle helicase in mitochondrial disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Using Atomic Force Microscopy to Study the Real Time Dynamics of DNA Unwinding by Mitochondrial Twinkle Helicase.Bio-protocol · 2021Article
- Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase.The Journal of biological chemistry · 2020Article
- History of DNA Helicases.Genes · 2020Review
- Structural basis for adPEO-causing mutations in the mitochondrial TWINKLE helicase.Human molecular genetics · 2019Article
- Inherited mitochondrial genomic instability and chemical exposures.Toxicology · 2017Review
- Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases.Ageing research reviews · 2017Review
- Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance.Frontiers in molecular biosciences · 2017Review
- Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease.Cold Spring Harbor molecular case studies · 2016Article
- Human mitochondrial DNA replication machinery and disease.Current opinion in genetics & development · 2016Review
- Novel subcellular localization of the DNA helicase Twinkle at the kinetochore complex during mitosis in neuronal-like progenitor cells.Histochemistry and cell biology · 2016Article
- Structure, function and evolution of the animal mitochondrial replicative DNA helicase.Critical reviews in biochemistry and molecular biology · 2016Review
- Mitochondrial DNA maintenance: an appraisal.Molecular and cellular biochemistry · 2015Review
- Borrowing nuclear DNA helicases to protect mitochondrial DNA.International journal of molecular sciences · 2015Review
- The hexameric structure of the human mitochondrial replicative helicase Twinkle.Nucleic acids research · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Missense mutations in the human C10orf2 gene, encoding the mitochondrial DNA (mtDNA) helicase, co-segregate with mitochondrial diseases such as adult-onset progressive external ophthalmoplegia, hepatocerebral syndrome with mtDNA depletion syndrome, and infantile-onset spinocerebellar ataxia. To understand the biochemical consequences of C10orf2 mutations, we overproduced wild type and 20 mutant forms of human mtDNA helicase in Escherichia coli and developed novel schemes to purify the recombinant enzymes to near homogeneity. A combination of molecular crowding, non-ionic detergents, Mg(2+) ions, and elevated ionic strength was required to combat insolubility and intrinsic instability of certain mutant variants. A systematic biochemical assessment of the enzymes included analysis of DNA binding affinity, DNA helicase activity, the kinetics of nucleotide hydrolysis, and estimates of thermal stability. In contrast to other studies, we found that all 20 mutant variants retain helicase function under optimized in vitro conditions despite partial reductions in DNA binding affinity, nucleotide hydrolysis, or thermal stability for some mutants. Such partial defects are consistent with the delayed presentation of mitochondrial diseases associated with mutation of C10orf2.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.