ArticleNucleic acids research2004
Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA.
Article in Nucleic acids research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 126 citations in OpenAlex.
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Primase promotes the competition between transcription and replication on the same template strand resulting in DNA damage.Nature communications · 2024Article
- Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells.Nucleic acids research · 2023Article
- Perspectives on formaldehyde dysregulation: Mitochondrial DNA damage and repair in mammalian cells.DNA repair · 2021Review
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- Thermodynamic analysis of DNA hybridization signatures near mitochondrial DNA deletion breakpoints.iScience · 2021Article
- Unbiased PCR-free spatio-temporal mapping of the mtDNA mutation spectrum reveals brain region-specific responses to replication instability.BMC biology · 2020Article
- Roles of the mitochondrial replisome in mitochondrial DNA deletion formation.Genetics and molecular biology · 2020Article
- ATAD3 controls mitochondrial cristae structure in mouse muscle, influencing mtDNA replication and cholesterol levels.Journal of cell science · 2018Article
- The mitochondrial DNA polymerase gamma degrades linear DNA fragments precluding the formation of deletions.Nature communications · 2018Article
- Linear mitochondrial DNA is rapidly degraded by components of the replication machinery.Nature communications · 2018Article
- Potential relationship between the biological effects of low-dose irradiation and mitochondrial ROS production.Journal of radiation research · 2018Review
- Review
- Probing the structural and molecular basis of nucleotide selectivity by human mitochondrial DNA polymerase γ.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Are mutagenic non D-loop direct repeat motifs in mitochondrial DNA under a negative selection pressure?Nucleic acids research · 2015Article
- Disturbed mitochondrial dynamics and neurodegenerative disorders.Nature reviews. Neurology · 2015Review
- Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease.Human molecular genetics · 2014Article
- Minireview: DNA replication in plant mitochondria.Mitochondrion · 2014Review
- DNA sequences proximal to human mitochondrial DNA deletion breakpoints prevalent in human disease form G-quadruplexes, a class of DNA structures inefficiently unwound by the mitochondrial replicative Twinkle helicase.The Journal of biological chemistry · 2014Article
- Twinkle mutations in two Chinese families with autosomal dominant progressive external ophthalmoplegia.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2014Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal dominant and/or recessive progressive external ophthalmoplegia (ad/arPEO) is associated with mtDNA mutagenesis. It can be caused by mutations in three nuclear genes, encoding the adenine nucleotide translocator 1, the mitochondrial helicase Twinkle or DNA polymerase gamma (POLG). How mutations in these genes result in progressive accumulation of multiple mtDNA deletions in post- mitotic tissues is still unclear. A recent hypothesis suggested that mtDNA replication infidelity could promote slipped mispairing, thereby stimulating deletion formation. This hypothesis predicts that mtDNA of ad/arPEO patients will contain frequent mutations throughout; in fact, our analysis of muscle from ad/arPEO patients revealed an age-dependent, enhanced accumulation of point mutations in addition to deletions, but specifically in the mtDNA control region. Both deleted and non-deleted mtDNA molecules showed increased point mutation levels, as did mtDNAs of patients with a single mtDNA deletion, suggesting that point mutations do not cause multiple deletions. Deletion breakpoint analysis showed frequent breakpoints around homopolymeric runs, which could be a signature of replication stalling. Therefore, we propose replication stalling as the principal cause of deletion formation.
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