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Publication : Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice.

First Author  Takai H Year  2000
Journal  Genes Dev Volume  14
Issue  12 Pages  1439-47
PubMed ID  10859163 Mgi Jnum  J:62918
Mgi Id  MGI:1860048 Doi  10.1101/gad.14.12.1439
Citation  Takai H, et al. (2000) Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice. Genes Dev 14(12):1439-47
abstractText  The recent discovery of checkpoint kinases has suggested the conservation of checkpoint mechanisms between yeast and mammals. In yeast, the protein kinase Chk1 is thought to mediate signaling associated with the DNA damage checkpoint of the cell cycle. However, the function of Chk1 in mammals has remained unknown. Targeted disruption of Chk1 in mice showed that Chk1(-/-) embryos exhibit gross morphologic abnormalities in nuclei as early as the blastocyst stage. In culture, Chk1(-/-) blastocysts showed a severe defect in outgrowth of the inner cell mass and died of apoptosis. DNA replication block and DNA damage failed to arrest the cell cycle before initiation of mitosis in Chk1(-/-) embryos. These results may indicate that Chk1 is indispensable for cell proliferation and survival through maintaining the G(2) checkpoint in mammals.
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