The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles

Abstract

The clock gene period-4 ( prd-4 ) in Neurospora was identified by a single allele displaying shortened circadian period and altered temperature compensation. Positional cloning followed by functional tests show that PRD-4 is an ortholog of mammalian checkpoint kinase 2 ( Chk2 ). Expression of prd-4 is regulated by the circadian clock and, reciprocally, PRD-4 physically interacts with the clock component FRQ, promoting its phosphorylation. DNA-damaging agents can reset the clock in a manner that depends on time of day, and this resetting is dependent on PRD-4. Thus, prd-4 , the Neurospora Chk2 , identifies a molecular link that feeds back conditionally from circadian output to input and the cell cycle.