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

• DOI: 10.1126/sciadv.abf8631
• Publication Date: 2021-07-02T19:24:11Z
• Authors: Min Jiang; Xie Xie; Xuefeng Zhu; Shan Jiang; Dusanka Milenkovic; Jelena Misic; Yonghong Shi; Nirwan Tandukar; Xinping Li; Ilian Atanassov; Louise Jenninger; Emily Hoberg; Sara Albarran-Gut...; Zsolt Szilagyi; Bertil Macao; Stefan J. Siira; Valerio Carelli; Jack D. Griffith; Claes M. Gustafsson; Thomas J. Nicholls; Aleksandra Filipo...; Nils-Göran Larsson; Maria Falkenberg
• Keywords: Primer (cosmetics); Transcription

We report a role for the mitochondrial single-stranded DNA binding protein (mtSSB) in regulating (mtDNA) replication initiation mammalian mitochondria. Transcription from light-strand promoter (LSP) is required both gene expression and generating RNA primers needed of mtDNA synthesis. In absence mtSSB, transcription LSP strongly up-regulated, but no are formed. Using deep sequencing mouse knockout model biochemical reconstitution experiments with pure proteins, we find that mtSSB necessary to restrict optimize primer formation at origins replication. Last, show human pathological versions causing severe disease cannot efficiently support