Cell cycle controls in fission yeast cells
description
Transcript of Cell cycle controls in fission yeast cells
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Cell cycle controls in fission yeast cells
Attila Csikasz-Nagy
Budapest University of Technology and Economics
Caltech, 27/03/2001
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Cytoplasmic cycle Chromosomal cycle
Cell cycle
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APC
Cdk
cyclinCdk +
misaligned chromosomes
chromosome segregation
cyclin destruction
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+Chromosome segregation
DNA replication
Cdk
cyclin
APC
-inactivates
degrades
APC & Cdk antagonism creates two cell cycle states
+
+
+
+
G1 phase
late mitosis
G2 & early mitosis
S phase
-
+
cellmass
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binding(fast)
AA
Nu
cleu
s+
degradedcyclin
ACT
Inactive Active
Cdk
cyclin
Cdk+
APC APC
Cdk
cyclincyclin
Cdkk1
k2
k4
k3
d APCdt =
(k3’ + k3” . ACT) (1 - APC) J3 + 1 - APC -
(k4’ + k4” . CDK) APC J4 + APC
d CDK dt = k1
. mass - [v2’ (1- APC) + v2” . APC) ] . CDK
mass
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The phaseplane portrait
AP
C
CDK
stable node
Stable node
saddle point
G1
S/M
CDK = k1
. mass v2’ (1 - APC) + v2” . APC
CDK = (k3’ + k3” . ACT ) (1 - APC)
k4” . APC .
J4 + APC J3 + 1 - APC -
k4’k4”
CDK nullcline:
APC nullcline:
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0
0.2
0.4
0.6
0.8
1
1.2
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.60
0.2
0.4
0.6
0.8
1
1.2
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
0
0.2
0.4
0.6
0.8
1
1.2
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.60
0.2
0.4
0.6
0.8
1
1.2
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
CDK
CDK CDK
CDK
AP
C
AP
C
AP
C
AP
C
mass = 1ACT = 0
mass = 2ACT = 1.5
mass = 1.75ACT = 0.3
mass = 1.6ACT = 0
G1
S/M S/M
G1 G1
S/M
A B
CD
Cell Growth
Aligned chromosomes
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CK
I
degradedcyclin
+
Cdkcyclin
CdkC
KI
Cdkcyclin
k1
k2
Inactive ActiveAPC APC
k4
k3
k5
k6
ACT
CK
I
degradedCKI
mass
+
+
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0
0.25
0.5
0.75
0 0.25 0.5 0.75
0
0.25
0.5
0.75
0 0.25 0.5 0.75
S/G2/MS/G2/M
G1
CKI total
CD
K t
otal
CDK totalnullcline
CD
K t
otal
CKI total
CKInullcline
pre-Start post-Start
Cell Growth
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P
degradedcyclin
Cdk
cyclin
Cdk
Inactive ActiveAPC APC
+
Cdk
cyclinP
P
k4
k3
k1
k2
k25
k25r
kw
kwr
kwee k25
+ +
+
ACT
mass
cdc25wee1 wee1 cdc25
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0
0.4
0.8
1.2
1.6
2
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
CDKA
CD
KT
Cdkcyclin
Cdkcyclin
P
MCell GrowthS/G2
G1
S/G2 M
M
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Cdc20
Nucleus
cyclin
Cdk
AA
The negative feedback loop
IE IE-P
+APCCdk
cyclinCdk
ACT
ACT inactive
active
unalignedchromosomes
mass
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Cdk
cyclin
CKIAPC
Wee1Mik1
wild type
ACT
0 50 100 150 2000.0
0.5
1.0
1.5
0.0
0.5
1.0
1.0
1.5
2.0
mass
G1 S+G2+M G1 S+G2+M
APC
CK
I
Cdk
cyclin
P Cdk
cyclin
cyclin
G1
G2
M
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Cdk
cyclin
CKIAPC
Mik1
wee1-
ACT
0 100 200 3000.0
0.5
0
1
0.5
1.0
APC
CK
I
mass
Cdk
cyclinP
Cdk
cyclin
G1 S+G2+M G1 S+G2+M
G1
G2
M
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Cdk
cyclin
CKIAPC
ACT
wee1- cdc25
no positivefeedback in G2
G1
M
2
3
0 100 200 3000
1
0
1APC
mass
Cdk
cyclinP
Cdk
cyclin
ACT
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Experimental data
Birth size (m)
6 8 10 12 14 16 18
Cycle tim
e (min)
0
50
100
150
200
250
300
350
Cell number
0 20 40 60 80
Cycle tim
e (min)
0
50
100
150
200
250
300
350
Simulation results
6 8 10 12 14 16 18
Cycle tim
e (min)
0
50
100
150
200
250
300
350
Cell number
0 10 20 30 40 50 60
Cycle tim
e (min)
0
50
100
150
200
250
300
350
Birth size (m)
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0.01 0.1 1 10 100 1000 10000
1
10
100
1000
0.4
3.0
WT
Cdc25 activity (%)
Wee
1 ac
tivity
(%
) cdc
cut
wee
quantiz
ed
cdc2cdc13
P cdc2cdc13
cdc25
wee1
Robustness of the model
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Bela NovakAkos Sveiczer Bela GyorffyZsuzsa Pataki
John TysonKathy Chen
Budapest University of Technology and Economics