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CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos
OBJECTIVES: DNA damage and errors of accurate chromosome segregation lead to aneuploidy and foetal defects. DNA repair and the spindle assembly checkpoint (SAC) are the mechanisms developed to protect from these defects. Checkpoint kinase 1 (CHK1) is reported to be an important DNA damage response p...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574881/ https://www.ncbi.nlm.nih.gov/pubmed/32914523 http://dx.doi.org/10.1111/cpr.12895 |
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author | Ju, Jia‐Qian Li, Xiao‐Han Pan, Meng‐Hao Xu, Yao Sun, Ming‐Hong Xu, Yi Sun, Shao‐Chen |
author_facet | Ju, Jia‐Qian Li, Xiao‐Han Pan, Meng‐Hao Xu, Yao Sun, Ming‐Hong Xu, Yi Sun, Shao‐Chen |
author_sort | Ju, Jia‐Qian |
collection | PubMed |
description | OBJECTIVES: DNA damage and errors of accurate chromosome segregation lead to aneuploidy and foetal defects. DNA repair and the spindle assembly checkpoint (SAC) are the mechanisms developed to protect from these defects. Checkpoint kinase 1 (CHK1) is reported to be an important DNA damage response protein in multiple models, but its functions remain unclear in early mouse embryos. MATERIALS AND METHODS: Immunofluorescence staining, immunoblotting and real‐time reverse transcription polymerase chain reaction were used to perform the analyses. Reactive oxygen species levels and Annexin‐V were also detected. RESULTS: Loss of CHK1 activity accelerated progress of the cell cycle at the first cleavage; however, it disturbed the development of early embryos to the morula/blastocyst stages. Further analysis indicated that CHK1 participated in spindle assembly and chromosome alignment, possibly due to its regulation of kinetochore‐microtubule attachment and recruitment of BubR1 and p‐Aurora B to the kinetochores, indicating its role in SAC activity. Loss of CHK1 activity led to embryonic DNA damage and oxidative stress, which further induced early apoptosis and autophagy, indicating that CHK1 is responsible for interphase DNA damage repair. CONCLUSIONS: Our results indicate that CHK1 is a key regulator of the SAC and DNA damage repair during early embryonic development in mice. |
format | Online Article Text |
id | pubmed-7574881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75748812020-10-23 CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos Ju, Jia‐Qian Li, Xiao‐Han Pan, Meng‐Hao Xu, Yao Sun, Ming‐Hong Xu, Yi Sun, Shao‐Chen Cell Prolif Original Articles OBJECTIVES: DNA damage and errors of accurate chromosome segregation lead to aneuploidy and foetal defects. DNA repair and the spindle assembly checkpoint (SAC) are the mechanisms developed to protect from these defects. Checkpoint kinase 1 (CHK1) is reported to be an important DNA damage response protein in multiple models, but its functions remain unclear in early mouse embryos. MATERIALS AND METHODS: Immunofluorescence staining, immunoblotting and real‐time reverse transcription polymerase chain reaction were used to perform the analyses. Reactive oxygen species levels and Annexin‐V were also detected. RESULTS: Loss of CHK1 activity accelerated progress of the cell cycle at the first cleavage; however, it disturbed the development of early embryos to the morula/blastocyst stages. Further analysis indicated that CHK1 participated in spindle assembly and chromosome alignment, possibly due to its regulation of kinetochore‐microtubule attachment and recruitment of BubR1 and p‐Aurora B to the kinetochores, indicating its role in SAC activity. Loss of CHK1 activity led to embryonic DNA damage and oxidative stress, which further induced early apoptosis and autophagy, indicating that CHK1 is responsible for interphase DNA damage repair. CONCLUSIONS: Our results indicate that CHK1 is a key regulator of the SAC and DNA damage repair during early embryonic development in mice. John Wiley and Sons Inc. 2020-09-10 /pmc/articles/PMC7574881/ /pubmed/32914523 http://dx.doi.org/10.1111/cpr.12895 Text en © 2020 The Authors. Cell Proliferation published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Ju, Jia‐Qian Li, Xiao‐Han Pan, Meng‐Hao Xu, Yao Sun, Ming‐Hong Xu, Yi Sun, Shao‐Chen CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos |
title | CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos |
title_full | CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos |
title_fullStr | CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos |
title_full_unstemmed | CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos |
title_short | CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos |
title_sort | chk1 monitors spindle assembly checkpoint and dna damage repair during the first cleavage of mouse early embryos |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574881/ https://www.ncbi.nlm.nih.gov/pubmed/32914523 http://dx.doi.org/10.1111/cpr.12895 |
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