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The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication
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- Jiang, M. (author)
- Karolinska Institutet
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- Xie, Xie (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Zhu, Xuefeng (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Milenkovic, D. (author)
- Misic, J. (author)
- Tandukar, N. (author)
- Li, X. (author)
- Atanassov, I. (author)
- Albarran-Gutierrez, S. (author)
- Siira, S. J. (author)
- Carelli, V. (author)
- Griffith, J. D. (author)
- Nicholls, T. J. (author)
- Filipovska, A. (author)
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- (creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2021
- 2021
- English.
- In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:27
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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. © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- DNA
- Mammals
- Mitochondria
- RNA
- Transcription
- Mitochondrial disease
- Mitochondrial DNA (mtDNA)
- Replication initiation
- RNA primers
- Single-stranded dna binding proteins
- Transcription initiation
- Proteins
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Jiang, M.
- Xie, Xie
- Zhu, Xuefeng
- Jiang, S.
- Milenkovic, D.
- Misic, J.
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- Shi, Yonghong
- Tandukar, N.
- Li, X.
- Atanassov, I.
- Jenninger, Louis ...
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- Szilagyi, Zsolt
- Macao, Bertil, 1 ...
- Siira, S. J.
- Carelli, V.
- Griffith, J. D.
- Gustafsson, Clae ...
- Nicholls, T. J.
- Filipovska, A.
- Larsson, N. G.
- Falkenberg, Mari ...
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