Boddy M N, Furnari B, Mondesert O, Russell P
Departments of Molecular Biology and Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
Science. 1998 May 8;280(5365):909-12. doi: 10.1126/science.280.5365.909.
Cdc2, the kinase that induces mitosis, is regulated by checkpoints that couple mitosis to the completion of DNA replication and repair. The repair checkpoint kinase Chk1 regulates Cdc25, a phosphatase that activates Cdc2. Effectors of the replication checkpoint evoked by hydroxyurea (HU) are unknown. Treatment of fission yeast with HU stimulated the kinase Cds1, which appears to phosphorylate the kinase Wee1, an inhibitor of Cdc2. The protein kinase Cds1 was also required for a large HU-induced increase in the amount of Mik1, a second inhibitor of Cdc2. HU-induced arrest of cell division was abolished in cds1 chk1 cells. Thus, Cds1 and Chk1 appear to jointly enforce the replication checkpoint.
Cdc2是一种诱导有丝分裂的激酶，它受检查点调控，这些检查点将有丝分裂与DNA复制及修复的完成联系起来。修复检查点激酶Chk1调节Cdc25，Cdc25是一种激活Cdc2的磷酸酶。羟基脲（HU）引发的复制检查点的效应因子尚不清楚。用HU处理裂殖酵母会刺激激酶Cds1，Cds1似乎会磷酸化激酶Wee1，Wee1是Cdc2的一种抑制剂。蛋白激酶Cds1对于HU诱导的Cdc2的另一种抑制剂Mik1的量大幅增加也是必需的。在cds1 chk1细胞中，HU诱导的细胞分裂停滞被消除。因此，Cds1和Chk1似乎共同执行复制检查点功能。
