DNA damage-activated kinase Chk2 is independent of proliferation or differentiation yet correlates with tissue biology

The Chk2 kinase is a tumor suppressor and key transducer of DNA-damage chec kpoints, We show that the human Chk2 protein is relatively stable, nuclear, and responding to gamma -radiation throughout the cell cycle. Contrary to the retinoblastoma protein-regulated, labile Chk1 kinase restricted to S-G, phases, Chk2 remains activatable even in quiescent and differentiating cel ls. In human tissues, Chk2 is homogeneously expressed in renewing cell popu lations such as epidermis or intestine, heterogeneous in conditionally rene wing tissues, and absent or cytoplasmic in static tissues such as muscle or brain. These data highlight striking differences between Chk2 and Chk1 and show unexpected correlation of Chk2 expression with tissue biology.