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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

445 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 language	English
Pages (from-to)	1439-1447
Number of pages	9
Journal	Genes and Development
Volume	14
Issue number	12
Publication status	Published - 2000 Jun 15

Keywords

Abnormal nuclei
Apoptosis
Chk1
Embryonic lethality
G checkpoints

ASJC Scopus subject areas

Genetics
Developmental Biology

Cite this

@article{2930520a695e4fa094e449cf243f43ea,

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.",

keywords = "Abnormal nuclei, Apoptosis, Chk1, Embryonic lethality, G checkpoints",

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 Nakayama, {Kei Ichi}",

year = "2000",

month = jun,

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, Kei Ichi

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.

KW - Abnormal nuclei

KW - Apoptosis

KW - Chk1

KW - Embryonic lethality

KW - G checkpoints

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

SN - 0890-9369

VL - 14

SP - 1439

EP - 1447

JO - Genes and Development

JF - Genes and Development

IS - 12

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Other files and links

Fingerprint

Cite this