title: Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity.
abstract: When prototrophic yeast cells are cultured under nutrient-limited conditions that mimic growth in the wild, rather than in the high-glucose solutions used in most laboratory studies, they exhibit a robustly periodic metabolic cycle. Over a cycle of 4 to 5 hours, yeast cells rhythmically alternate between glycolysis and respiration. The cell division cycle is tightly constrained to the reductive phase of this yeast metabolic cycle, with DNA replication taking place only during the glycolytic phase. We show that cell cycle mutants impeded in metabolic cycle-directed restriction of cell division exhibit substantial increases in spontaneous mutation rate. In addition, disruption of the gene encoding a DNA checkpoint kinase that couples the cell division cycle to the circadian cycle abolishes synchrony of the metabolic and cell cycles. Thus, circadian, metabolic, and cell division cycles may be coordinated similarly as an evolutionarily conserved means of preserving genome integrity.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Odstrcil
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Tu
authors.forename: Steven L
authors.initials: SL
authors.lastname: McKnight
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D064447:Checkpoint Kinase 2; D004261:DNA Replication; D016681:Genome, Fungal; D006019:Glycolysis; D006706:Homeostasis; D006861:Hydrogen Peroxide / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D008715:Methionine / Q000378:metabolism; D010084:Oxidation-Reduction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C115052:SML1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D008715:Methionine; D006861:Hydrogen Peroxide; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae