Model of correlation between cellular localization and function of Chk1. The inner and outer circles represent the nucleus and cytoplasm, respectively. Cytoplasmic Chk1 mutants (dashed ovals) exhibit a significantly accelerated pace of nuclear export, leaving them little time to accumulate in the nucleus to be phosphorylated by ATR or to perform functions essential for cell viability and, to a lesser extent, checkpoints. In the meantime, the mutant form of Chk1 in the cytoplasm is unstable, causing the reduction of the total level of the Chk1 mutant in the cells. The arrow thickness roughly indicates the intensity of events. The dashed arrow indicates functional defects. See “Discussion” for more detail.