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CHK1 monitors spindle assembly checkpoint and DNA damage repair during the first cleavage of mouse early embryos.
- Source :
-
Cell Proliferation . Oct2020, Vol. 53 Issue 10, p1-12. 12p. - Publication Year :
- 2020
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09607722
- Volume :
- 53
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Cell Proliferation
- Publication Type :
- Academic Journal
- Accession number :
- 146527016
- Full Text :
- https://doi.org/10.1111/cpr.12895