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

113 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

Keywords

  • Cdc27
  • DT40
  • Mitotic cyclin
  • P27
  • Rapamycin

ASJC Scopus subject areas

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

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