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

Hiroyuki Takai, Kaoru Tominaga, Noboru Motoyama, Yohji A. Minamishima, Hiroyasu Nagahama, Tadasuke Tsukiyama, Kyoji Ikeda, Keiko Nakayama, Makoto Nakanishi, Kei Ichi Nakayama

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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 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 G2 checkpoint in mammals.

Original languageEnglish
Pages (from-to)1439-1447
Number of pages9
JournalGenes and Development
Volume14
Issue number12
Publication statusPublished - 2000 Jun 15

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Keywords

  • Abnormal nuclei
  • Apoptosis
  • Chk1
  • Embryonic lethality
  • G checkpoints

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Takai, H., Tominaga, K., Motoyama, N., Minamishima, Y. A., Nagahama, H., Tsukiyama, T., Ikeda, K., Nakayama, K., Nakanishi, M., & Nakayama, K. I. (2000). Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice. Genes and Development, 14(12), 1439-1447.