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Cell cycle localization dynamics of mitochondrial DNA polymerase IC in African trypanosomes

Trypanosoma brucei has a unique catenated mitochondrial DNA (mtDNA) network called kinetoplast DNA (kDNA). Replication of kDNA occurs once per cell cycle in near synchrony with nuclear S phase and requires the coordination of many proteins. Among these are three essential DNA polymerases (TbPOLIB, I...

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Autores principales: Concepción-Acevedo, Jeniffer, Miller, Jonathan C., Boucher, Michael J., Klingbeil, Michele M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254582/
https://www.ncbi.nlm.nih.gov/pubmed/30133333
http://dx.doi.org/10.1091/mbc.E18-02-0127
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author Concepción-Acevedo, Jeniffer
Miller, Jonathan C.
Boucher, Michael J.
Klingbeil, Michele M.
author_facet Concepción-Acevedo, Jeniffer
Miller, Jonathan C.
Boucher, Michael J.
Klingbeil, Michele M.
author_sort Concepción-Acevedo, Jeniffer
collection PubMed
description Trypanosoma brucei has a unique catenated mitochondrial DNA (mtDNA) network called kinetoplast DNA (kDNA). Replication of kDNA occurs once per cell cycle in near synchrony with nuclear S phase and requires the coordination of many proteins. Among these are three essential DNA polymerases (TbPOLIB, IC, and ID). Localization dynamics of these proteins with respect to kDNA replication stages and how they coordinate their functions during replication are not well understood. We previously demonstrated that TbPOLID undergoes dynamic localization changes that are coupled to kDNA replication events. Here, we report the localization of TbPOLIC, a second essential DNA polymerase, and demonstrate the accumulation of TbPOLIC foci at active kDNA replication sites (antipodal sites) during stage II of the kDNA duplication cycle. While TbPOLIC was undetectable by immunofluorescence during other cell cycle stages, steady-state protein levels measured by Western blot remained constant. TbPOLIC foci colocalized with the fraction of TbPOLID that localized to the antipodal sites. However, the partial colocalization of the two essential DNA polymerases suggests a highly dynamic environment at the antipodal sites to coordinate the trafficking of replication proteins during kDNA synthesis. These data indicate that cell cycle–dependent localization is a major regulatory mechanism for essential mtDNA polymerases during kDNA replication.
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spelling pubmed-62545822019-02-04 Cell cycle localization dynamics of mitochondrial DNA polymerase IC in African trypanosomes Concepción-Acevedo, Jeniffer Miller, Jonathan C. Boucher, Michael J. Klingbeil, Michele M. Mol Biol Cell Articles Trypanosoma brucei has a unique catenated mitochondrial DNA (mtDNA) network called kinetoplast DNA (kDNA). Replication of kDNA occurs once per cell cycle in near synchrony with nuclear S phase and requires the coordination of many proteins. Among these are three essential DNA polymerases (TbPOLIB, IC, and ID). Localization dynamics of these proteins with respect to kDNA replication stages and how they coordinate their functions during replication are not well understood. We previously demonstrated that TbPOLID undergoes dynamic localization changes that are coupled to kDNA replication events. Here, we report the localization of TbPOLIC, a second essential DNA polymerase, and demonstrate the accumulation of TbPOLIC foci at active kDNA replication sites (antipodal sites) during stage II of the kDNA duplication cycle. While TbPOLIC was undetectable by immunofluorescence during other cell cycle stages, steady-state protein levels measured by Western blot remained constant. TbPOLIC foci colocalized with the fraction of TbPOLID that localized to the antipodal sites. However, the partial colocalization of the two essential DNA polymerases suggests a highly dynamic environment at the antipodal sites to coordinate the trafficking of replication proteins during kDNA synthesis. These data indicate that cell cycle–dependent localization is a major regulatory mechanism for essential mtDNA polymerases during kDNA replication. The American Society for Cell Biology 2018-10-15 /pmc/articles/PMC6254582/ /pubmed/30133333 http://dx.doi.org/10.1091/mbc.E18-02-0127 Text en © 2018 Concepción-Acevedo et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Concepción-Acevedo, Jeniffer
Miller, Jonathan C.
Boucher, Michael J.
Klingbeil, Michele M.
Cell cycle localization dynamics of mitochondrial DNA polymerase IC in African trypanosomes
title Cell cycle localization dynamics of mitochondrial DNA polymerase IC in African trypanosomes
title_full Cell cycle localization dynamics of mitochondrial DNA polymerase IC in African trypanosomes
title_fullStr Cell cycle localization dynamics of mitochondrial DNA polymerase IC in African trypanosomes
title_full_unstemmed Cell cycle localization dynamics of mitochondrial DNA polymerase IC in African trypanosomes
title_short Cell cycle localization dynamics of mitochondrial DNA polymerase IC in African trypanosomes
title_sort cell cycle localization dynamics of mitochondrial dna polymerase ic in african trypanosomes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254582/
https://www.ncbi.nlm.nih.gov/pubmed/30133333
http://dx.doi.org/10.1091/mbc.E18-02-0127
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