Committing to mitosis

There is a time for caution and a time for committing. For the cell cycle, a halt before mitosis is an appropriate response to ionizing radiation or inhibition of DNA replication. But once mitosis is underway the cell is better off just carrying on regardless of DNA-damaging insults. Dmitry Bulavin, Albert Fornace (National Cancer Institute [NCI], Bethesda, MD), and colleagues now report on a double phosphorylation switch that keeps irradiated mitotic cells from bouncing unexpectedly out of mitosis.

The switch is in one of the Cdc25 phosphatases—proteins that remove an inhibitory phosphate from Cdc2, thus allowing entry into mitosis. Cdc25C is itself phosphorylated during interphase. First, a constitutive kinase and then an irradiation-induced kinase hit Ser 216 on Cdc25, thus keeping the phosphatase inactive. The NCI team now show that this...