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yeast cell. cell wall (protection) cell membrane (import + export, signaling) cytoplasm (energy production, growth) nucleus (heredity). material and energy. What is a cell?. A. D. Feeding + excreting. B. E. C. Y. signaling. Shape change. move. What cells can do?. DNA. DNA. DNA.
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yeast cell cell wall (protection) cell membrane (import + export, signaling) cytoplasm (energy production, growth) nucleus (heredity) material and energy What is a cell?
A D Feeding + excreting B E C Y signaling Shape change move What cells can do?
DNA DNA DNA DNA DNA replication RNA genetic code DNA protein + RNA DNA DNA Transcription The information flow in cells (central dogma) DNA
xerox machine collating machine DNA cell division DNA replication chromosome segregation
The central dogma gene transcript protein S P metabolism
Beyond the central dogma genome transcriptome proteome networks S P metabolome
G1 G2
Cdk CycBM Cdk CycBS MPF SPF
G1 G2 Cdk CycBM Cdk CycBS G2/M MPF exit SPF Start
control box cell division DNA replication chromosome segregation
reversible Tyrosine phosphorylation ubiquitin dependent proteolysis binding of a stoichiometric inhibitor
cytoplasmic mass doubling time G1 G2 Cdk CycBM Cdk CycBS G2/M MPF exit SPF Start
Balanced growth and division - - + + + viability cytoplasmic mass doubling time M M M G2 G2 S cycle time (min) G2 G2 M G1 S S G2 G1 G1 S S G1 G1 wee1- cki- cdc25 - WT cki– wee1-
Balanced growth and division - - + + + viability M M M G2 G2 cell volume at division (fl) S cycle time (min) G2 G2 M G1 S S G2 G1 G1 S S G1 G1 WT wee1- cki- cki– wee1- cdc25 -
pheromone - G1 G2 Cdk CycBM Cdk CycBS MPF SPF
inhibitor - G1 G2 Cdk CycBM Cdk CycBS MPF SPF Start
inhibitor G1 G2 Cdk CycBM Cdk CycBS - G2/M MPF SPF Start
cell mass doubling time G1 G2 + + exit G2/M Cdk CycB Start
inactive inactive APCM Wee1 P delay Exit Wee1 APCM P Cdk Cdk CycB Cdc25 P APCG1 Cdc25 G2/M inactive Cdk APCG1 inactive CKI CycB P CKI CKI AA Start CycB AA Cdk Cdk CycB inactive
Parameters? ? fission yeast budding yeast
Mutants in Fission Yeast gene viability trait cdc2-no block in G1 and G2 cdc13-no endoreplication rum1-yes sterile ste9-yes sterile wee1- yes small cells cdc25- no block in G2 cdc2opyes wt cdc13opyes wt rum1opno endoreplication ste9opno endoreplication wee1op yes large cells cdc25op yes small cells wee1- rum1 no extremely small wee1- cdc25 yes quantized cycles wee1- cdc25op no mitotic catastrophe
period of oscillation period time tD CKI APCM mass (m) Cdk CycB APCG1 = cycle time = mass doubling time (tD) dm/dt = m where = ln2/tD CycB M G1 S/G2 M rate ~ mass time (min)
period period time tD CKI APCG1 mass (m) Cdk CycB APCM Size control over the cell cycle mass dm/dt = m where = ln2/tD CycB M G1 S/G2 M rate ~ mass time (min)
APCM Wee1 P Cdk/CycB delay Exit Wee1 APCM cell mass P Cdk/CycB Cdk Cdk CycB Cdc25 P APCG1 cell mass Cdc25 Cdk APCG1 CKI CycB Cdk/CycB P CKI CKI AA Start cell mass CycB AA Cdk Cdk CycB G2/M
Bifurcation diagram of the cell cycle control network stable s.s. unstable s.s. min/max M Cdk/CycB S/G2 G1 cell mass
newborn cell dividingcell Cell cycle regulation on the bifurcation diagram stable s.s. unstable s.s. min/max M Cdk/CycB Exit G2/M S/G2 Start G1 cell mass
G1 checkpoint M 0.4 Cdk/CycB S/G2 G1 0 0 2 3 5 1 4 cell mass metaphase checkpoint G2 checkpoint 1.6 M M 1.2 0.4 Exit G2/M Cdk/CycB Cdk/CycB 0.8 S/G2 0.4 G1 G1 S/G2 0 0 0 2 3 5 1 4 4 0 2 3 5 1 cell mass cell mass Checkpoint controls