ArticleThe Journal of biological chemistry2014
Mapping topoisomerase sites in mitochondrial DNA with a poisonous mitochondrial topoisomerase I (Top1mt).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- The low endoribonuclease activity and lack of rNMP preference of human mitochondrial topoisomerase 1 protect against ribonucleotide-dependent deletions.Nucleic acids research · 2025Article
- Genome-wide Mapping of Topoisomerase Binding Sites Suggests Topoisomerase 3α (TOP3A) as a Reader of Transcription-Replication Conflicts (TRC).bioRxiv : the preprint server for biology · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Deficiency of TOP1MT enhances glycolysis through the stimulation of PDK4 expression in gastric cancer.Cancer & metabolism · 2024Article
- Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT.Human molecular genetics · 2023Article
- Two type I topoisomerases maintain DNA topology in human mitochondria.Nucleic acids research · 2022Article
- Functional characterization of two variants of mitochondrial topoisomerase TOP1MT that impact regulation of the mitochondrial genome.The Journal of biological chemistry · 2022Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- A comprehensive pan-cancer analysis of the expression characteristics, prognostic value, and immune characteristics ofFrontiers in genetics · 2022Article
- Mitochondrial topoisomerase 1 inhibition induces topological DNA damage and T cell dysfunction in patients with chronic viral infection.Frontiers in cellular and infection microbiology · 2022Article
- Controlling the topology of mammalian mitochondrial DNA.Open biology · 2021Review
- SCAN1-TDP1 trapping on mitochondrial DNA promotes mitochondrial dysfunction and mitophagy.Science advances · 2019Article
- Replication Stress at Telomeric and Mitochondrial DNA: Common Origins and Consequences on Ageing.International journal of molecular sciences · 2019Review
- Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair.International journal of molecular sciences · 2019Review
- Twist and Turn-Topoisomerase Functions in Mitochondrial DNA Maintenance.International journal of molecular sciences · 2019Review
- Genome-wide mapping of Topoisomerase I activity sites reveal its role in chromosome segregation.Nucleic acids research · 2019Article
- Transcription profiling suggests that mitochondrial topoisomerase IB acts as a topological barrier and regulator of mitochondrial DNA transcription.The Journal of biological chemistry · 2017Article
- Distribution bias and biochemical characterization of TOP1MT single nucleotide variants.Scientific reports · 2017Article
- Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage.Science advances · 2017Article
- Dynamic Effects of Topoisomerase I Inhibition on R-Loops and Short Transcripts at Active Promoters.PloS one · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial topoisomerase I (Top1mt) is a type IB topoisomerase present in vertebrates and exclusively targeted to mitochondria. Top1mt relaxes mitochondrial DNA (mtDNA) supercoiling by introducing transient cleavage complexes wherein the broken DNA strand swivels around the intact strand. Top1mt cleavage complexes (Top1mtcc) can be stabilized in vitro by camptothecin (CPT). However, CPT does not trap Top1mtcc efficiently in cells and is highly cytotoxic due to nuclear Top1 targeting. To map Top1mtcc on mtDNA in vivo and to overcome the limitations of CPT, we designed two substitutions (T546A and N550H) in Top1mt to stabilize Top1mtcc. We refer to the double-mutant enzyme as Top1mt*. Using retroviral transduction and ChIP-on-chip assays with Top1mt* in Top1mt knock-out murine embryonic fibroblasts, we demonstrate that Top1mt* forms high levels of cleavage complexes preferentially in the noncoding regulatory region of mtDNA, accumulating especially at the heavy strand replication origin OH, in the ribosomal genes (12S and 16S) and at the light strand replication origin OL. Expression of Top1mt* also caused rapid mtDNA depletion without affecting mitochondria mass, suggesting the existence of specific mitochondrial pathways for the removal of damaged mtDNA.
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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 OpenQuestion graph.