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, Keiichi Nakayama

Research output: Contribution to journalArticle

408 Citations (Scopus)

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 - Jun 15 2000

Fingerprint

Cell Cycle Checkpoints
Mammals
Blastocyst
DNA Damage
Embryonic Structures
Yeasts
DNA Replication
Mitosis
Cell Survival
Phosphotransferases
Cell Proliferation
Apoptosis

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Cite this

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

Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice. / Takai, Hiroyuki; Tominaga, Kaoru; Motoyama, Noboru; Minamishima, Yohji A.; Nagahama, Hiroyasu; Tsukiyama, Tadasuke; Ikeda, Kyoji; Nakayama, Keiko; Nakanishi, Makoto; Nakayama, Keiichi.

In: Genes and Development, Vol. 14, No. 12, 15.06.2000, p. 1439-1447.

Research output: Contribution to journalArticle

Takai, H, Tominaga, K, Motoyama, N, Minamishima, YA, Nagahama, H, Tsukiyama, T, Ikeda, K, Nakayama, K, Nakanishi, M & Nakayama, K 2000, 'Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice', Genes and Development, vol. 14, no. 12, pp. 1439-1447.
Takai H, Tominaga K, Motoyama N, Minamishima YA, Nagahama H, Tsukiyama T et al. Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice. Genes and Development. 2000 Jun 15;14(12):1439-1447.
Takai, Hiroyuki ; Tominaga, Kaoru ; Motoyama, Noboru ; Minamishima, Yohji A. ; Nagahama, Hiroyasu ; Tsukiyama, Tadasuke ; Ikeda, Kyoji ; Nakayama, Keiko ; Nakanishi, Makoto ; Nakayama, Keiichi. / Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice. In: Genes and Development. 2000 ; Vol. 14, No. 12. pp. 1439-1447.
@article{d718a0f0bc6b489f88a3eca79255a7ec,
title = "Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice",
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.",
author = "Hiroyuki Takai and Kaoru Tominaga and Noboru Motoyama and Minamishima, {Yohji A.} and Hiroyasu Nagahama and Tadasuke Tsukiyama and Kyoji Ikeda and Keiko Nakayama and Makoto Nakanishi and Keiichi Nakayama",
year = "2000",
month = "6",
day = "15",
language = "English",
volume = "14",
pages = "1439--1447",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "12",

}

TY - JOUR

T1 - Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice

AU - Takai, Hiroyuki

AU - Tominaga, Kaoru

AU - Motoyama, Noboru

AU - Minamishima, Yohji A.

AU - Nagahama, Hiroyasu

AU - Tsukiyama, Tadasuke

AU - Ikeda, Kyoji

AU - Nakayama, Keiko

AU - Nakanishi, Makoto

AU - Nakayama, Keiichi

PY - 2000/6/15

Y1 - 2000/6/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034659341&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034659341&partnerID=8YFLogxK

M3 - Article

C2 - 10859163

AN - SCOPUS:0034659341

VL - 14

SP - 1439

EP - 1447

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 12

ER -