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The FANCM family Mph1 helicase localizes to the mitochondria and contributes to mtDNA stability
Institution:1. CNRS UMR8200 – Genetic Stability and Oncogenesis, Université Paris-Sud, Paris-Saclay, Institut Gustave Roussy, Villejuif, France;2. Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;1. Laboratory of Molecular Biology and DNA Repair, Department of Medicine, University of Udine, Udine, 33100, Italy;2. Laboratory of Bioenergetics, Department of Medicine, University of Udine, Udine, 33100, Italy;3. Institute of Medical Genetics, Department of Medicine, University of Udine, Udine, 33100, Italy;4. Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University, School of Medicine, Indianapolis, IN 46202, USA;5. Herman B Wells Center for Pediatric Research, Department of Pediatrics and Pharmacology & Toxicology, Indiana University, School of Medicine, Indianapolis, IN 46202, USA;6. General Surgery and Transplantation Unit, Department of Medicine, University of Udine, Udine, 33100, Italy;7. Laboratory of Immunology, Department of Medicine, University of Udine, Udine, 33100, Italy;1. Department of Pharmacological Sciences, Stony Brook University, Renaissance School of Medicine, Basic Science Tower 8-140, Stony Brook, New York, 11794, USA;2. Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC, 27709-2233, USA;3. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA;1. Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250062, China;2. Department of Cancer Biology, Cardinal Bernardin Cancer Center, Loyola University Chicago Stritch School of Medicine, Maywood, IL, 60153, United States;1. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Laboratory Center, Erling Skjalgssons gate 1, 7491, Trondheim, Norway;2. St. Olavs Hospital, Trondheim University Hospital, Clinic of Medicine, Postboks 3250 Sluppen, 7006, Trondheim, Norway;3. Department of Biomedicine, University of Bergen, Bergen, Norway;4. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden;1. Center for Gene Regulation in Health and Disease and Department of Biological Sciences, Cleveland State University, Cleveland, OH 44115, USA;2. Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA;3. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA;4. Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
Abstract:Mitochondria are membrane-bound organelles found in eukaryotic cells where they generate energy through the respiratory chain. They contain their own genome that encodes genes critical to the mitochondrial function, but most of their protein content is synthetized from nuclear encoded genes. Damages to the mtDNA can cause mutations and rearrangements with an impact on the respiratory functions of the cell. DNA repair factors are able to localize to mitochondria to restore mtDNA integrity and ensure its proper inheritance. We describe in this article the mitochondrial localization of the Mph1/FANCM helicase that serves critical roles in nuclear DNA repair processes. Mph1 localizes to mitochondria and its functions contribute to the mtDNA integrity under mtDNA damaging conditions.
Keywords:Mitochondrial DNA repair  Helicase Mph1  Fanconi Anemia-like pathway  Double-strand break  Homologous recombination
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