The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication.

Autor:	Jiang M; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China.; Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Xie X; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden., Zhu X; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden., Jiang S; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden., Milenkovic D; Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Misic J; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden., Shi Y; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden., Tandukar N; Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27514, USA., Li X; Proteomics Core Facility, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Atanassov I; Proteomics Core Facility, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Jenninger L; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden., Hoberg E; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden., Albarran-Gutierrez S; Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Szilagyi Z; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden., Macao B; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden., Siira SJ; Harry Perkins Institute of Medical Research and ARC Centre of Excellence in Synthetic Biology, Nedlands, WA 6009, Australia.; Telethon Kids Institute, Northern Entrance, Perth Children's Hospital, 15 Hospital Avenue, Nedlands, WA, Australia., Carelli V; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.; IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma di Neurogenetica, Bologna, Italy., Griffith JD; Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27514, USA., Gustafsson CM; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden., Nicholls TJ; Wellcome Centre for Mitochondrial Research, Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK., Filipovska A; Harry Perkins Institute of Medical Research and ARC Centre of Excellence in Synthetic Biology, Nedlands, WA 6009, Australia.; Telethon Kids Institute, Northern Entrance, Perth Children's Hospital, 15 Hospital Avenue, Nedlands, WA, Australia., Larsson NG; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden. nils-goran.larsson@ki.se maria.falkenberg@medkem.gu.se., Falkenberg M; Department of Medical Biochemistry and Cell Biology, University of Gothenburg, PO Box 440, Gothenburg 405 30, Sweden. nils-goran.larsson@ki.se maria.falkenberg@medkem.gu.se.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Jul 02; Vol. 7 (27). Date of Electronic Publication: 2021 Jul 02 (Print Publication: 2021).
DOI:	10.1126/sciadv.abf8631
Abstrakt:	We report a role for the mitochondrial single-stranded DNA binding protein (mtSSB) in regulating mitochondrial DNA (mtDNA) replication initiation in mammalian mitochondria. Transcription from the light-strand promoter (LSP) is required both for gene expression and for generating the RNA primers needed for initiation of mtDNA synthesis. In the absence of mtSSB, transcription from LSP is strongly up-regulated, but no replication primers are formed. Using deep sequencing in a mouse knockout model and biochemical reconstitution experiments with pure proteins, we find that mtSSB is necessary to restrict transcription initiation to optimize RNA primer formation at both origins of mtDNA replication. Last, we show that human pathological versions of mtSSB causing severe mitochondrial disease cannot efficiently support primer formation and initiation of mtDNA replication. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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