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The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes

Rad51 is a conserved eukaryotic protein that mediates the homologous recombination repair of DNA double-strand breaks that occur during mitosis and meiosis. In addition, Rad51 promotes mitochondrial DNA synthesis when replication stress is increased. Rad51 also regulates cell cycle progression by pr...

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Autores principales: Kim, Kyeoung-Hwa, Park, Ji-Hoon, Kim, Eun-Young, Ko, Jung-Jae, Park, Kyung-Soon, Lee, Kyung-Ah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039699/
https://www.ncbi.nlm.nih.gov/pubmed/27677401
http://dx.doi.org/10.1038/srep34110
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author Kim, Kyeoung-Hwa
Park, Ji-Hoon
Kim, Eun-Young
Ko, Jung-Jae
Park, Kyung-Soon
Lee, Kyung-Ah
author_facet Kim, Kyeoung-Hwa
Park, Ji-Hoon
Kim, Eun-Young
Ko, Jung-Jae
Park, Kyung-Soon
Lee, Kyung-Ah
author_sort Kim, Kyeoung-Hwa
collection PubMed
description Rad51 is a conserved eukaryotic protein that mediates the homologous recombination repair of DNA double-strand breaks that occur during mitosis and meiosis. In addition, Rad51 promotes mitochondrial DNA synthesis when replication stress is increased. Rad51 also regulates cell cycle progression by preserving the G2/M transition in embryonic stem cells. In this study, we report a novel function of Rad51 in regulating mitochondrial activity during in vitro maturation of mouse oocytes. Suppression of Rad51 by injection of Rad51 dsRNA into germinal vesicle-stage oocytes resulted in arrest of meiosis in metaphase I. Rad51-depleted oocytes showed chromosome misalignment and failures in spindle aggregation, affecting the completion of cytokinesis. We found that Rad51 depletion was accompanied by decreased ATP production and mitochondrial membrane potential and increased DNA degradation. We further demonstrated that the mitochondrial defect activated autophagy in Rad51-depleted oocytes. Taken together, we concluded that Rad51 functions to safeguard mitochondrial integrity during the meiotic maturation of oocytes.
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spelling pubmed-50396992016-09-30 The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes Kim, Kyeoung-Hwa Park, Ji-Hoon Kim, Eun-Young Ko, Jung-Jae Park, Kyung-Soon Lee, Kyung-Ah Sci Rep Article Rad51 is a conserved eukaryotic protein that mediates the homologous recombination repair of DNA double-strand breaks that occur during mitosis and meiosis. In addition, Rad51 promotes mitochondrial DNA synthesis when replication stress is increased. Rad51 also regulates cell cycle progression by preserving the G2/M transition in embryonic stem cells. In this study, we report a novel function of Rad51 in regulating mitochondrial activity during in vitro maturation of mouse oocytes. Suppression of Rad51 by injection of Rad51 dsRNA into germinal vesicle-stage oocytes resulted in arrest of meiosis in metaphase I. Rad51-depleted oocytes showed chromosome misalignment and failures in spindle aggregation, affecting the completion of cytokinesis. We found that Rad51 depletion was accompanied by decreased ATP production and mitochondrial membrane potential and increased DNA degradation. We further demonstrated that the mitochondrial defect activated autophagy in Rad51-depleted oocytes. Taken together, we concluded that Rad51 functions to safeguard mitochondrial integrity during the meiotic maturation of oocytes. Nature Publishing Group 2016-09-28 /pmc/articles/PMC5039699/ /pubmed/27677401 http://dx.doi.org/10.1038/srep34110 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kim, Kyeoung-Hwa
Park, Ji-Hoon
Kim, Eun-Young
Ko, Jung-Jae
Park, Kyung-Soon
Lee, Kyung-Ah
The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes
title The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes
title_full The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes
title_fullStr The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes
title_full_unstemmed The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes
title_short The role of Rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes
title_sort role of rad51 in safeguarding mitochondrial activity during the meiotic cell cycle in mammalian oocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039699/
https://www.ncbi.nlm.nih.gov/pubmed/27677401
http://dx.doi.org/10.1038/srep34110
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