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p21 provides stage specific DNA damage control to preimplantation embryos

Oncogene volume 26, pages 6141–6149 (2007)Cite this article

Abstract

The early stage embryogenesis of higher eukaryotes lacks some of the damage response pathways such as G1/S checkpoint, G2/M checkpoint and apoptosis. We examined here the damage response of preimplantation stage embryos after fertilization with 6 Gy irradiated sperm. Sperm-irradiated embryos developed normally for the first 2.5 days, but started to exhibit a developmental delay at day 3.5. p21 was activated in the delayed embryos, which carried numerous micronuclei owing to delayed chromosome instability. Apoptosis was observed predominantly in the inner cell mass of the day 4.0 embryos. Sperm-irradiated p21−/− embryos lacked the delay, but chromosome instability and apoptosis were more pronounced than the corresponding p21 wild-type embryos. We conclude from the result that damage responses come in a stage-specific manner during preimplantation stage development; p53-dependent S checkpoint at the zygote stage, p21-mediated cell cycle arrest at the morula/blastocyst stages and apoptosis after the blastocyst stage in the inner cell mass.

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Acknowledgements

SKA is the recipient of Japan Society for the Promotion of Science (JSPS) fellowship (ID: P02268). This work was supported by Grant-in-Aid from the Ministry of Education, Science, Sports, Culture and Technology (MEXT), Japan to ON The work was also supported by a grant from the Nuclear Safety Research Association, Tokyo.

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Authors and Affiliations

  1. Kasturba Medical College, Manipal, India

    S K Adiga & P Kumar

  2. Kyoto University Radiation Biology Center, Sakyo-ku, Kyoto, Japan

    M Toyoshima, J Takeda, M Taga, H Nagai & O Niwa

  3. The Research Institute for Advanced Science and Technology, Osaka Prefecture University, Sakai, Osaka, Japan

    K Shiraishi

  4. Genome Damage Response Research Unit, RIKEN, 2-1 Hirosawa, Wako Saitama, Japan

    T Shimura

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  1. S K Adiga
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  2. M Toyoshima
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Correspondence to O Niwa.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Adiga, S., Toyoshima, M., Shiraishi, K. et al. p21 provides stage specific DNA damage control to preimplantation embryos. Oncogene 26, 6141–6149 (2007). https://doi.org/10.1038/sj.onc.1210444

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