title: Checkpoints couple transcription network oscillator dynamics to cell-cycle progression.
abstract: BACKGROUND
  The coupling of cyclin dependent kinases (CDKs) to an intrinsically oscillating network of transcription factors has been proposed to control progression through the cell cycle in budding yeast, Saccharomyces cerevisiae. The transcription network regulates the temporal expression of many genes, including cyclins, and drives cell-cycle progression, in part, by generating successive waves of distinct CDK activities that trigger the ordered program of cell-cycle events. Network oscillations continue autonomously in mutant cells arrested by depletion of CDK activities, suggesting the oscillator can be uncoupled from cell-cycle progression. It is not clear what mechanisms, if any, ensure that the network oscillator is restrained when progression in normal cells is delayed or arrested. A recent proposal suggests CDK acts as a master regulator of cell-cycle processes that have the potential for autonomous oscillatory behavior.
  
  
  RESULTS
  Here we find that mitotic CDK is not sufficient for fully inhibiting transcript oscillations in arrested cells. We do find that activation of the DNA replication and spindle assembly checkpoints can fully arrest the network oscillator via overlapping but distinct mechanisms. Further, we demonstrate that the DNA replication checkpoint effector protein, Rad53, acts to arrest a portion of transcript oscillations in addition to its role in halting cell-cycle progression.
  
  
  CONCLUSIONS
  Our findings indicate that checkpoint mechanisms, likely via phosphorylation of network transcription factors, maintain coupling of the network oscillator to progression during cell-cycle arrest.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Bristow
authors.forename: Adam R
authors.initials: AR
authors.lastname: Leman
authors.forename: Laura A
authors.initials: LA
authors.lastname: Simmons Kovacs
authors.forename: Anastasia
authors.initials: A
authors.lastname: Deckard
authors.forename: John
authors.initials: J
authors.lastname: Harer
authors.forename: Steven B
authors.initials: SB
authors.lastname: Haase
mesh_terms: D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D053263:Gene Regulatory Networks; D059566:M Phase Cell Cycle Checkpoints; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: C093749:CLB2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D064447:Checkpoint Kinase 2; D016203:CDC2 Protein Kinase; C067022:RAD53 protein, S cerevisiae