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 journalArticle

109 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 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.

Original languageEnglish
Pages (from-to)6499-6508
Number of pages10
JournalEMBO Journal
Volume20
Issue number22
DOIs
Publication statusPublished - 2001 Nov 15
Externally publishedYes

Fingerprint

Anaphase-Promoting Complex-Cyclosome
G1 Phase Cell Cycle Checkpoints
DNA Damage
Vertebrates
Cyclins
Chemical activation
Cells
Cdh1 Proteins
Yeast
Cdc20 Proteins
Drosophila
DNA
Yeasts
Cyclin G1
G1 Phase
Sirolimus
Mitosis
Chickens
Cell Cycle
Clone Cells

Keywords

  • Cdc27
  • DT40
  • Mitotic cyclin
  • P27
  • Rapamycin

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells. / Sudo, Tamotsu; Ota, Yosuke; Kotani, Shuji; Nakao, Mitsuyoshi; Takami, Yasunari; Takeda, Shunichi; Saya, Hideyuki.

In: EMBO Journal, Vol. 20, No. 22, 15.11.2001, p. 6499-6508.

Research output: Contribution to journalArticle

Sudo, Tamotsu ; Ota, Yosuke ; Kotani, Shuji ; Nakao, Mitsuyoshi ; Takami, Yasunari ; Takeda, Shunichi ; Saya, Hideyuki. / Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells. In: EMBO Journal. 2001 ; Vol. 20, No. 22. pp. 6499-6508.
@article{74d3fae70c0d4b7b90b7dbdb1f8b5c67,
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.",
keywords = "Cdc27, DT40, Mitotic cyclin, P27, Rapamycin",
author = "Tamotsu Sudo and Yosuke Ota and Shuji Kotani and Mitsuyoshi Nakao and Yasunari Takami and Shunichi Takeda and Hideyuki Saya",
year = "2001",
month = "11",
day = "15",
doi = "10.1093/emboj/20.22.6499",
language = "English",
volume = "20",
pages = "6499--6508",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "22",

}

TY - JOUR

T1 - Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells

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.

KW - Cdc27

KW - DT40

KW - Mitotic cyclin

KW - P27

KW - Rapamycin

UR - http://www.scopus.com/inward/record.url?scp=0035890165&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035890165&partnerID=8YFLogxK

U2 - 10.1093/emboj/20.22.6499

DO - 10.1093/emboj/20.22.6499

M3 - Article

VL - 20

SP - 6499

EP - 6508

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 22

ER -