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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.
Sudo, T., Ota, Y., Kotani, S., Nakao, M., Takami, Y., Takeda, S. and Saya
EMBO J 20: 6499-6508, 2001
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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 the chicken DT40 cells disrupted in their Cdh1 loci. Cdh1 was dispensable for viability and cell cycle progression. However, as similar to yeast and Drosophila, loss of Cdh1 induced unscheduled accumulation of mitotic cyclins in G1, resulting in abrogation of G1 arrest caused by treatment withrapamycin, an inducer of p27kip1. Furthermore, we found that Cdh1-/- cells fail to maintain DNA-damage induced G2 arrest and that Cdh1-APC is activated by X-radiation-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. PMID: 11707420 [PubMed - as supplied by publisher]
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