Mammalian never-in-mitosis-related kinase 1 in control of faithful chromatid segregation

Protein kinases are fundamental participants in the response to DNA damage from ionizing radiation and other insults. The molecular roles of the PI3-like kinases ATM and ATR have been well characterized in the cascade of events that detect damaged DNA, activate cell cycle checkpoints, orchestrate and amplify mediators of the response, and ensure that damaged DNA is repaired before cells divide. Another mammalian protein kinase, NEK1 (never-in-mitosis related kinase 1), has similarly important but distinct roles in DNA damage responses. Studies in vitro, in cells, and in animals indicate that NEK1 functions uniquely as a sensor and mediator of the response to DNA damage. NEK1 is important for limiting cell death after DNA damage, activating S-phase and mitotic checkpoints properly, ensuring faithful chromosome segregation, and preventing specific neoplastic diseases. Data suggest that NEK1 deserves to be investigated further in exploring the mechanisms that lead to aneuploidy, aberrant cell death, and uncontrolled proliferation in human diseases such as kidney cancer, lymphomas, polycystic kidney disease, and bone diseases.