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Cell cycle controls in fission yeast cells. Attila Csikasz-Nagy Budapest University of Technology and Economics. Caltech, 27/03/2001. Cell cycle. Cytoplasmic cycle. Chromosomal cycle. chromosome segregation. misaligned chromosomes. APC. Cdk. +. Cdk. cyclin destruction. cyclin. Cdk.

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slide1

Cell cycle controls in fission yeast cells

Attila Csikasz-Nagy

Budapest University of Technology and Economics

Caltech, 27/03/2001

slide2

Cell cycle

Cytoplasmic cycle

Chromosomal cycle

slide3

chromosome segregation

misaligned chromosomes

APC

Cdk

+

Cdk

cyclin destruction

cyclin

slide4

Cdk

cyclin

APC & Cdk antagonism creates two cell cycle states

S phase

DNA replication

+

cell

mass

+

degrades

G2 & early mitosis

G1 phase

-

-

inactivates

+

APC

+

+

+

Chromosome segregation

late mitosis

slide5

ACT

k3

Active

Inactive

APC

APC

k4

+

+

Cdk

Cdk

cyclin

k2

Nucleus

degraded

cyclin

Cdk

k1

Cdk

cyclin

AA

cyclin

mass

binding

(fast)

slide6

The phaseplane portrait

G1

APC

stable node

saddle point

S/M

Stable node

CDK nullcline:

CDK

APC nullcline:

slide7

A

B

G1

APC

APC

mass = 1

ACT = 0

mass = 1.6

ACT = 0

Cell Growth

S/M

S/M

CDK

CDK

D

C

G1

G1

APC

APC

mass = 1.75

ACT = 0.3

mass = 2

ACT = 1.5

Aligned chromosomes

S/M

CDK

CDK

slide8

Cdk

cyclin

CKI

Cdk

cyclin

CKI

CKI

ACT

k3

Active

Inactive

APC

APC

k4

+

Cdk

+

k1

k2

mass

degraded

cyclin

+

k5

degraded

CKI

k6

slide9

pre-Start

post-Start

S/G2/M

CDK total

nullcline

S/G2/M

CDK total

CDK total

Cell Growth

CKI

nullcline

G1

CKI total

CKI total

slide10

Cdk

cyclin

Cdk

cyclin

ACT

k3

Inactive

Active

APC

APC

k4

+

+

Cdk

k1

k2

mass

degraded

cyclin

+

+

kwee

k25

kw

k25

wee1

wee1

cdc25

cdc25

P

kwr

k25r

P

P

slide11

M

S/G2

M

Cell Growth

S/G2

M

Cdk

cyclin

P

G1

Cdk

cyclin

CDKT

CDKA

slide12

The negative feedback loop

Nucleus

Cdc20

ACT

inactive

unaligned

chromosomes

IE

IE-P

ACT

active

+APC

Cdk

Cdk

cyclin

Cdk

mass

cyclin

AA

slide13

APC

P

CKI

Cdk

Cdk

cyclin

cyclin

wild type

G1

S+G2+M

G1

S+G2+M

mass

ACT

M

Cdk

Wee1

Mik1

G2

cyclin

G1

CKI

APC

cyclin

slide14

APC

P

CKI

Cdk

Cdk

cyclin

cyclin

wee1-

G1

S+G2+M

G1

S+G2+M

mass

ACT

M

Cdk

G2

Mik1

cyclin

G1

CKI

APC

slide15

P

Cdk

Cdk

cyclin

cyclin

wee1- cdc25

mass

ACT

M

ACT

APC

no positive

feedback in G2

Cdk

cyclin

G1

CKI

APC

slide16

350

350

300

300

250

250

Experimental data

200

200

150

150

100

100

Cycle time (min)

Cycle time (min)

50

50

0

0

0

20

40

60

80

6

8

10

12

14

16

18

Cell number

Birth size (

m

m)

350

350

300

300

250

250

Simulationresults

200

200

150

150

100

100

Cycle time (min)

Cycle time (min)

50

50

0

0

6

8

10

12

14

16

18

0

10

20

30

40

50

60

Birth size (

m

m)

Cell number

slide17

cdc

WT

Wee1 activity (%)

wee

cut

quantized

Cdc25 activity (%)

Robustness of the model

wee1

P

cdc2

cdc2

cdc13

cdc13

cdc25

slide18

Budapest University of Technology and Economics

Bela Novak

Akos Sveiczer

Bela Gyorffy

Zsuzsa Pataki

John Tyson

Kathy Chen

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