Journal Article

Analysis of p53 Dependent Damage Response in Sperm-irradiated Mouse Embryos

Megumi Toyoshima

in Journal of Radiation Research

Volume 50, issue 1, pages 11-17
Published in print January 2009 | ISSN: 0449-3060
Published online January 2009 | e-ISSN: 1349-9157 | DOI: https://dx.doi.org/10.1269/jrr.08099
Analysis of p53 Dependent Damage Response in Sperm-irradiated Mouse Embryos

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  • Clinical Genetics
  • Molecular Biology and Genetics
  • Epidemiology
  • Radiology
  • Nuclear Chemistry, Photochemistry, and Radiation

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Ionizing radiation activates a series of DNA damage response, cell cycle checkpoints to arrest cells at G1/S, S and G2/M, DNA repair, and apoptosis. The DNA damage response is thought to be the major determinant of cellular radiosensitivity and thought to operate in all higher eukaryotic cells. However, the radiosensitivity is known to differ considerably during ontogeny of mammals and early embryos of mouse for example are much more sensitive to radiation than adults. We have focused on the radiation-induced damage response during pre-implantation stage of mouse embryo. Our study demonstrates a hierarchy of damage responses to assure the genomic integrity in early embryonic development. In the sperm-irradiated zygotes, p53 dependent S-phase checkpoint functions to suppress erroneous replication of damaged DNA. The transcription-dependent function is not required and the DNA-binging domain of the protein is essential for this p53 dependent S-phase checkpoint. p21 mediated cleavage arrest comes next during early embryogenesis to prevent delayed chromosome damage at morula/blastocyst stages. Apoptosis operates even later only in the cells of ICM at the blastocyst stage to eliminate deleterious cells. Thus, early development of sperm-irradiated embryos is protected at least by three mechanisms regulated by p53 and by p21.

Keywords: p53 dependent S-phase checkpoint; Mouse embryo; Pre-implantation; p53; p21; Apoptosis

Journal Article.  0 words. 

Subjects: Clinical Genetics ; Molecular Biology and Genetics ; Epidemiology ; Radiology ; Nuclear Chemistry, Photochemistry, and Radiation

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