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The novel surveillance mechanism of the Trp53-dependent s-phase checkpoint ensures chromosome damage repair and preimplantation-stage development of mouse embryos fertilized with x-irradiated sperm.
- Source :
-
Radiation research [Radiat Res] 2002 Dec; Vol. 158 (6), pp. 735-42. - Publication Year :
- 2002
-
Abstract
- Cell cycle checkpoints and apoptosis function as surveillance mechanisms in somatic tissues. However, some of these mechanisms are lacking or are restricted during the preimplantation stage. Previously, we reported the presence of a novel Trp53-dependent S-phase checkpoint that suppresses pronuclear DNA synthesis in mouse zygotes fertilized with X-irradiated sperm (sperm-irradiated zygotes) (Shimura et al., Mol. Cell. Biol. 22, 2220-2228, 2002). Here we studied the role of the Trp53-dependent S-phase checkpoint in the early stage of development of sperm-irradiated zygotes. In the Trp53(+/+) genetic background, all of the sperm-irradiated zygotes cleaved successfully to the two-cell stage despite the fact that half of them carried a sub-2N amount of DNA. These zygotes progressed normally to the eight-cell stage and then implanted, but the subsequent fetal development was suppressed in a dose-dependent manner. In contrast, sperm-irradiated Trp53(-/-) embryos lacking an S-phase checkpoint exhibited an abnormal segregation of chromosomes at the first cleavage, even though they carried an apparently normal 2N amount of DNA. They were morphologically abnormal with numerous micronuclei, and they degenerated before reaching the eight-cell stage. As a consequence, no implants were observed for sperm-irradiated Trp53(-/-) embryos. These results suggest that the Trp53-dependent S-phase checkpoint is a surveillance mechanism involved in the repair of chromosome damage and ensures the preimplantation-stage development of sperm-irradiated embryos.
- Subjects :
- Animals
DNA metabolism
Dose-Response Relationship, Radiation
Embryo, Mammalian radiation effects
Female
Fertilization radiation effects
Fetus radiation effects
G1 Phase radiation effects
G2 Phase radiation effects
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Micronucleus Tests
Microscopy, Fluorescence
Mitosis radiation effects
Placenta radiation effects
Spermatozoa radiation effects
Time Factors
DNA Damage
DNA Repair
Genes, p53 genetics
S Phase radiation effects
X-Rays
Subjects
Details
- Language :
- English
- ISSN :
- 0033-7587
- Volume :
- 158
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Radiation research
- Publication Type :
- Academic Journal
- Accession number :
- 12452776
- Full Text :
- https://doi.org/10.1667/0033-7587(2002)158[0735:tnsmot]2.0.co;2