Abstract
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 thatChk1−/− 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 inChk1−/− embryos. These results may indicate that Chk1 is indispensable for cell proliferation and survival through maintaining the G2 checkpoint in mammals.
Authors
10
- Hiroyuki Takai (first)
- Kaoru Tominaga (additional)
- Noboru Motoyama (additional)
- Yohji A. Minamishima (additional)
- Hiroyasu Nagahama (additional)
- Tadasuke Tsukiyama (additional)
- Kyoji Ikeda (additional)
- Keiko Nakayama (additional)
- Makoto Nakanishi (additional)
- Kei-ichi Nakayama (additional)
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Dates
Type | When |
---|---|
Created | 3 years, 9 months ago (Nov. 14, 2021, 10:32 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 10:33 p.m.) |
Indexed | 3 weeks, 5 days ago (July 27, 2025, 3:45 a.m.) |
Issued | 25 years, 2 months ago (June 15, 2000) |
Published | 25 years, 2 months ago (June 15, 2000) |
Published Online | 25 years, 2 months ago (June 15, 2000) |
Published Print | 25 years, 2 months ago (June 15, 2000) |
@article{Takai_2000, title={Aberrant cell cycle checkpoint function and early embryonic death in Chk1−/− mice}, volume={14}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.14.12.1439}, DOI={10.1101/gad.14.12.1439}, number={12}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Takai, Hiroyuki and Tominaga, Kaoru and Motoyama, Noboru and Minamishima, Yohji A. and Nagahama, Hiroyasu and Tsukiyama, Tadasuke and Ikeda, Kyoji and Nakayama, Keiko and Nakanishi, Makoto and Nakayama, Kei-ichi}, year={2000}, month=jun, pages={1439–1447} }