title: 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.
authors.affiliation: Department of Genetics, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: António M
authors.initials: AM
authors.lastname: Pregueiro
authors.forename: Qiuyun
authors.initials: Q
authors.lastname: Liu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Baker
authors.forename: Jay C
authors.initials: JC
authors.lastname: Dunlap
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Loros
mesh_terms: D000595:Amino Acid Sequence; D002453:Cell Cycle; D064447:Checkpoint Kinase 2; D002940:Circadian Rhythm; D003001:Cloning, Molecular; D004249:DNA Damage; D025461:Feedback, Physiological; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D009491:Neurospora / Q000201:enzymology* / Q000235:genetics; D009492:Neurospora crassa / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: C087405:FRQ protein, Neurospora crassa; D005656:Fungal Proteins; D008741:Methyl Methanesulfonate; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases