Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells

Tamotsu Sudo; Yosuke Ota; Shuji Kotani; Mitsuyoshi Nakao; Yasunari Takami; Shunichi Takeda; Hideyuki Saya

doi:10.1093/emboj/20.22.6499

Activation of Cdh1-dependent APC is required for G₁ cell cycle arrest and DNA damage-induced G₂ checkpoint in vertebrate cells

Tamotsu Sudo, Yosuke Ota, Shuji Kotani, Mitsuyoshi Nakao, Yasunari Takami, Shunichi Takeda, Hideyuki Saya

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

125 Citations (Scopus)

Abstract

Anaphase-promoting complex (APC) is activated by two regulatory proteins, Cdc20 and Cdh1. In yeast and Drosophila, Cdh1-dependent APC (Cdh1-APC) activity targets mitotic cyclins from the end of mitosis to the G₁ phase. To investigate the function of Cdh1 in vertebrate cells, we generated clones of chicken DT40 cells disrupted in their Cdh1 loci. Cdh1 was dispensable for viability and cell cycle progression. However, similarly to yeast and Drosophila, loss of Cdh1 induced unscheduled accumulation of mitotic cyclins in G₁, resulting in abrogation of G₁, arrest caused by treatment with rapamycin, an inducer of p27^Kipl. Furthermore, we found that Cdh1^-1- cells fail to maintain DNA damage-induced G₂ arrest and that Cdh1-APC is activated by X-irradiation-induced DNA damage. Thus, activation of Cdh1-APC plays a crucial role in both cdk inhibitor-dependent G₁ arrest and DNA damage-induced G₂ arrest.

Original language	English
Pages (from-to)	6499-6508
Number of pages	10
Journal	EMBO Journal
Volume	20
Issue number	22
DOIs	https://doi.org/10.1093/emboj/20.22.6499
Publication status	Published - 15-11-2001
Externally published	Yes

All Science Journal Classification (ASJC) codes

Neuroscience(all)
Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)

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title = "Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells",

abstract = "Anaphase-promoting complex (APC) is activated by two regulatory proteins, Cdc20 and Cdh1. In yeast and Drosophila, Cdh1-dependent APC (Cdh1-APC) activity targets mitotic cyclins from the end of mitosis to the G1 phase. To investigate the function of Cdh1 in vertebrate cells, we generated clones of chicken DT40 cells disrupted in their Cdh1 loci. Cdh1 was dispensable for viability and cell cycle progression. However, similarly to yeast and Drosophila, loss of Cdh1 induced unscheduled accumulation of mitotic cyclins in G1, resulting in abrogation of G1, arrest caused by treatment with rapamycin, an inducer of p27Kipl. Furthermore, we found that Cdh1-1- cells fail to maintain DNA damage-induced G2 arrest and that Cdh1-APC is activated by X-irradiation-induced DNA damage. Thus, activation of Cdh1-APC plays a crucial role in both cdk inhibitor-dependent G1 arrest and DNA damage-induced G2 arrest.",

author = "Tamotsu Sudo and Yosuke Ota and Shuji Kotani and Mitsuyoshi Nakao and Yasunari Takami and Shunichi Takeda and Hideyuki Saya",

year = "2001",

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AU - Sudo, Tamotsu

AU - Ota, Yosuke

AU - Kotani, Shuji

AU - Nakao, Mitsuyoshi

AU - Takami, Yasunari

AU - Takeda, Shunichi

AU - Saya, Hideyuki

PY - 2001/11/15

Y1 - 2001/11/15

N2 - Anaphase-promoting complex (APC) is activated by two regulatory proteins, Cdc20 and Cdh1. In yeast and Drosophila, Cdh1-dependent APC (Cdh1-APC) activity targets mitotic cyclins from the end of mitosis to the G1 phase. To investigate the function of Cdh1 in vertebrate cells, we generated clones of chicken DT40 cells disrupted in their Cdh1 loci. Cdh1 was dispensable for viability and cell cycle progression. However, similarly to yeast and Drosophila, loss of Cdh1 induced unscheduled accumulation of mitotic cyclins in G1, resulting in abrogation of G1, arrest caused by treatment with rapamycin, an inducer of p27Kipl. Furthermore, we found that Cdh1-1- cells fail to maintain DNA damage-induced G2 arrest and that Cdh1-APC is activated by X-irradiation-induced DNA damage. Thus, activation of Cdh1-APC plays a crucial role in both cdk inhibitor-dependent G1 arrest and DNA damage-induced G2 arrest.

AB - Anaphase-promoting complex (APC) is activated by two regulatory proteins, Cdc20 and Cdh1. In yeast and Drosophila, Cdh1-dependent APC (Cdh1-APC) activity targets mitotic cyclins from the end of mitosis to the G1 phase. To investigate the function of Cdh1 in vertebrate cells, we generated clones of chicken DT40 cells disrupted in their Cdh1 loci. Cdh1 was dispensable for viability and cell cycle progression. However, similarly to yeast and Drosophila, loss of Cdh1 induced unscheduled accumulation of mitotic cyclins in G1, resulting in abrogation of G1, arrest caused by treatment with rapamycin, an inducer of p27Kipl. Furthermore, we found that Cdh1-1- cells fail to maintain DNA damage-induced G2 arrest and that Cdh1-APC is activated by X-irradiation-induced DNA damage. Thus, activation of Cdh1-APC plays a crucial role in both cdk inhibitor-dependent G1 arrest and DNA damage-induced G2 arrest.

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Activation of Cdh1-dependent APC is required for G₁ cell cycle arrest and DNA damage-induced G₂ checkpoint in vertebrate cells

Abstract

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