The Neurospora checkpoint kinase 2: a regulatory link between the circadian and cell cycles.

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.

Assignment of an essential role for the Neurospora frequency gene in circadian entrainment to temperature cycles.

Circadian systems include slave oscillators and central pacemakers, and the cores of eukaryotic circadian clocks described to date are composed of transcription and translation feedback loops (TTFLs). In the model system Neurospora, normal circadian rhythmicity requires a TTFL in which a White Collar complex (WCC) activates expression of the frequency (frq) gene, and the FRQ protein feeds back to attenuate that activation. To further test the centrality of this TTFL to the circadian mechanism in Neurospora, we used low-amplitude temperature cycles to compare WT and frq-null strains under conditions in which a banding rhythm was elicited.