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In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication

Journal article
Authors Javier Miralles Fusté
Yonghong Shi
Sjoerd Wanrooij
Xuefeng Zhu
Elisabeth Jemt
Örjan Persson
N. Sabouri
Claes M Gustafsson
Maria Falkenberg
Published in Plos Genetics
Volume 10
Issue 12
ISSN 1553-7390
Publication year 2014
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Links dx.doi.org/10.1371/journal.pgen.100...
Keywords MOUSE L CELLS, RNA-POLYMERASE, MTDNA, TRANSCRIPTION, MUTATIONS, MECHANISM, TEMPLATE, REVEALS, TWINKLE, ORIGINS, Genetics & Heredity
Subject categories Cell and Molecular Biology

Abstract

Mitochondrial DNA (mtDNA) encodes for proteins required for oxidative phosphorylation, and mutations affecting the genome have been linked to a number of diseases as well as the natural ageing process in mammals. Human mtDNA is replicated by a molecular machinery that is distinct from the nuclear replisome, but there is still no consensus on the exact mode of mtDNA replication. We here demonstrate that the mitochondrial single-stranded DNA binding protein (mtSSB) directs origin specific initiation of mtDNA replication. MtSSB covers the parental heavy strand, which is displaced during mtDNA replication. MtSSB blocks primer synthesis on the displaced strand and restricts initiation of light-strand mtDNA synthesis to the specific origin of light-strand DNA synthesis (OriL). The in vivo occupancy profile of mtSSB displays a distinct pattern, with the highest levels of mtSSB close to the mitochondrial control region and with a gradual decline towards OriL. The pattern correlates with the replication products expected for the strand displacement mode of mtDNA synthesis, lending strong in vivo support for this debated model for mitochondrial DNA replication.

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Denna text är utskriven från följande webbsida:
http://gu.se/english/research/publication/?publicationId=212036
Utskriftsdatum: 2019-12-15