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Science 313 (5787): 644-649

Copyright © 2006 by the American Association for the Advancement of Science

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

António M. Pregueiro,1 Qiuyun Liu,3 Christopher L. Baker,1 Jay C. Dunlap,1* Jennifer J. Loros1,2*

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.

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} (J.C.D.); jennifer.loros{at} (J.J.L.)

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