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The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles
António M. Pregueiro,1Qiuyun Liu,3Christopher L. Baker,1Jay C. Dunlap,1*Jennifer J. Loros1,2*
The clock gene period-4 (prd-4) in Neurospora was identifiedby a single allele displaying shortened circadian period andaltered temperature compensation. Positional cloning followedby functional tests show that PRD-4 is an ortholog of mammaliancheckpoint kinase 2 (Chk2). Expression of prd-4 is regulatedby the circadian clock and, reciprocally, PRD-4 physically interactswith the clock component FRQ, promoting its phosphorylation.DNA-damaging agents can reset the clock in a manner that dependson time of day, and this resetting is dependent on PRD-4. Thus,prd-4, the Neurospora Chk2, identifies a molecular link thatfeeds back conditionally from circadian output to input andthe cell cycle.
1 Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA. 2 Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA. 3 The Key Laboratory of Gene Engineering of Ministry of Education and Biotechnology Research Center, Zhongshan University, Guangzhou 510275, P. R. China.
* To whom correspondence should be addressed. E-mail: jay.c.dunlap{at}dartmouth.edu (J.C.D.); jennifer.loros{at}dartmouth.edu (J.J.L.)
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