线粒体DNA
生物
底漆(化妆品)
DNA复制
抄写(语言学)
遗传学
分子生物学
复制的起源
细胞生物学
作者
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-Gutierrez,Zsolt Szilagyi,Bertil Macao,Stefan J. Siira,Valerio Carelli,Jack D. Griffith,Claes M. Gustafsson,Thomas J. Nicholls,Aleksandra Filipovska,Nils-Göran Larsson,Maria Falkenberg
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-07-02
卷期号:7 (27)
被引量:11
标识
DOI:10.1126/sciadv.abf8631
摘要
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.
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