In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication
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 re...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256270/ https://www.ncbi.nlm.nih.gov/pubmed/25474639 http://dx.doi.org/10.1371/journal.pgen.1004832 |
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author | Miralles Fusté, Javier Shi, Yonghong Wanrooij, Sjoerd Zhu, Xuefeng Jemt, Elisabeth Persson, Örjan Sabouri, Nasim Gustafsson, Claes M. Falkenberg, Maria |
author_facet | Miralles Fusté, Javier Shi, Yonghong Wanrooij, Sjoerd Zhu, Xuefeng Jemt, Elisabeth Persson, Örjan Sabouri, Nasim Gustafsson, Claes M. Falkenberg, Maria |
author_sort | Miralles Fusté, Javier |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4256270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42562702014-12-11 In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication Miralles Fusté, Javier Shi, Yonghong Wanrooij, Sjoerd Zhu, Xuefeng Jemt, Elisabeth Persson, Örjan Sabouri, Nasim Gustafsson, Claes M. Falkenberg, Maria PLoS Genet Research Article 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. Public Library of Science 2014-12-04 /pmc/articles/PMC4256270/ /pubmed/25474639 http://dx.doi.org/10.1371/journal.pgen.1004832 Text en © 2014 Fusté et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Miralles Fusté, Javier Shi, Yonghong Wanrooij, Sjoerd Zhu, Xuefeng Jemt, Elisabeth Persson, Örjan Sabouri, Nasim Gustafsson, Claes M. Falkenberg, Maria In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication |
title |
In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication |
title_full |
In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication |
title_fullStr |
In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication |
title_full_unstemmed |
In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication |
title_short |
In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication |
title_sort | in vivo occupancy of mitochondrial single-stranded dna binding protein supports the strand displacement mode of dna replication |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256270/ https://www.ncbi.nlm.nih.gov/pubmed/25474639 http://dx.doi.org/10.1371/journal.pgen.1004832 |
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