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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Cell Cycle*
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Checkpoint Kinase 2
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Circadian Rhythm*
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Cloning, Molecular
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DNA Damage
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Feedback, Physiological
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Fungal Proteins / chemistry
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Gene Expression Regulation, Fungal
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Genes, Fungal
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Methyl Methanesulfonate / pharmacology
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Molecular Sequence Data
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Mutation
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Neurospora / enzymology*
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Neurospora / genetics
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Neurospora crassa / cytology
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Neurospora crassa / enzymology*
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Neurospora crassa / physiology*
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Phosphorylation
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism*
Substances
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FRQ protein, Neurospora crassa
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Fungal Proteins
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Methyl Methanesulfonate
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Checkpoint Kinase 2
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Protein Serine-Threonine Kinases