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Lookup NU author(s): Dr Thomas NichollsORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
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.
Author(s): Jiang M, Xie X, Zhu X, Jiang S, Milenkovic D, Misic J, Shi Y, Tandukar N, Li X, Atanassov I, Jenninger L, Hoberg E, Albarran-Gutierrez S, Szilagyi Z, Macao B, Siira SJ, Carelli V, Griffith JD, Gustafsson CM, Nicholls TJ, Filipovska A, Larsson NG, Falkenberg M
Publication type: Article
Publication status: Published
Journal: Science Advances
Year: 2021
Volume: 7
Issue: 27
Online publication date: 02/07/2021
Acceptance date: 20/05/2021
Date deposited: 05/07/2021
ISSN (print): 2096-5958
ISSN (electronic): 2375-2548
Publisher: AAAS
URL: https://doi.org/10.1126/sciadv.abf8631
DOI: 10.1126/sciadv.abf8631
PubMed id: 34215584
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