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In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication
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In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication
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In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication
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Journal Article
In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication
2014
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ DNA
/ DNA, Mitochondrial - genetics
/ DNA, Mitochondrial - metabolism
/ DNA, Single-Stranded - metabolism
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ DNA-Directed DNA Polymerase - genetics
/ DNA-Directed DNA Polymerase - metabolism
/ DNA-Directed RNA Polymerases - genetics
/ DNA-Directed RNA Polymerases - metabolism
/ Genes
/ Genomes
/ Humans
/ Light
/ Mammals
/ Medicine and Health Sciences
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - metabolism
/ MTDNA
/ Mutation
/ ORIGINS
/ Proteins
/ REVEALS
/ TEMPLATE
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ TWINKLE
