Aberrant cell cycle checkpoint function and early embryonic death in Chk1−/− mice

Autor: Keiko Nakayama, Makoto Nakanishi, Kaoru Tominaga, Kyoji Ikeda, Hiroyuki Takai, Noboru Motoyama, Keiichi I. Nakayama, Hiroyasu Nagahama, Yohji A. Minamishima, Tadasuke Tsukiyama
Rok vydání: 2000
Předmět:
Zdroj: Genes & Development. 14:1439-1447
ISSN: 1549-5477
0890-9369
DOI: 10.1101/gad.14.12.1439
Popis: 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.
Databáze: OpenAIRE