ArticleNucleic acids research2009
A novel approach for organelle-specific DNA damage targeting reveals different susceptibility of mitochondrial DNA to the anticancer drugs camptothecin and topotecan.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Structure-Activity Relationship of FL118 Platform Position 7 Versus Position 9-Derived Compounds and Their Mechanism of Action and Antitumor Activity.Journal of medicinal chemistry · 2023Article
- Evolution of TOP1 and TOP1MT Topoisomerases in Chordata.Journal of molecular evolution · 2023Article
- Phytochemical Targeting of Mitochondria for Breast Cancer Chemoprevention, Therapy, and Sensitization.International journal of molecular sciences · 2022Review
- 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
- Emerging Roles and Mechanisms of lncRNA FOXD3-AS1 in Human Diseases.Frontiers in oncology · 2022Review
- Etoposide and Camptothecin Reduce Growth, Viability, the Generation ofIndian journal of microbiology · 2021Article
- Does the Poly (ADP-Ribose) Polymerase Inhibitor Veliparib Merit Further Study for Cancer-Associated Weight Loss? Observations and Conclusions from Sixty Prospectively Treated Patients.Journal of palliative medicine · 2018Article
- Camptothecin induces GOncotarget · 2018Article
- Topoisomerases as anticancer targets.The Biochemical journal · 2018Review
- DNA topoisomerase-targeting chemotherapeutics: what's new?Cancer chemotherapy and pharmacology · 2017Review
- Formation of Nitrogenase NifDK Tetramers in the Mitochondria of Saccharomyces cerevisiae.ACS synthetic biology · 2017Article
- Expression of a functional oxygen-labile nitrogenase component in the mitochondrial matrix of aerobically grown yeast.Nature communications · 2016Article
- Chronically elevated glucose compromises myocardial mitochondrial DNA integrity by alteration of mitochondrial topoisomerase function.American journal of physiology. Cell physiology · 2011Article
- Tumor physiology and charge dynamics of anticancer drugs: implications for camptothecin-based drug development.Current medicinal chemistry · 2011Article
- Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA.Nucleic acids research · 2009Article
- DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition.Chemical reviews · 2009Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA is susceptible of being damaged by chemicals, UV light or gamma irradiation. Nuclear DNA damage invokes both a checkpoint and a repair response. By contrast, little is known about the cellular response to mitochondrial DNA damage. We designed an experimental system that allows organelle-specific DNA damage targeting in Saccharomyces cerevisiae. DNA damage is mediated by a toxic topoisomerase I allele which leads to the formation of persistent DNA single-strand breaks. We show that organelle-specific targeting of a toxic topoisomerase I to either the nucleus or mitochondria leads to nuclear DNA damage and cell death or to loss of mitochondrial DNA and formation of respiration-deficient 'petite' cells, respectively. In wild-type cells, toxic topoisomerase I-DNA intermediates are formed as a consequence of topoisomerase I interaction with camptothecin-based anticancer drugs. We reasoned that targeting of topoisomerase I to the mitochondria of top1 Delta cells should lead to petite formation in the presence of camptothecin. Interestingly, camptothecin failed to generate petite; however, its derivative topotecan accumulates in mitochondria and induces petite formation. Our findings demonstrate that drug modifications can lead to organelle-specific DNA damage and thus opens new perspectives on the role of mitochondrial DNA-damage in cancer treatment.
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