yeast cell

What is a cell?

material and

energy

cell wall (protection)

cell membrane (import + export, signaling)

cytoplasm (energy production, growth)

nucleus (heredity)

What cells can do?

move

Shape change

A

B

CE

DFeeding + excreting

signaling

Y

The information flow in cells (central dogma)

DNA

DNA

DNA

DNADNA

DNA replication

+

DNA

DNA

RNA

RNA

DNA

Transcription

genetic code

protein

DNA replication

cell

division

chromosomesegregation

xeroxmachine

DNA

collatingmachine

The central dogma

S P

gene

transcript

protein

metabolism

genome

transc

ripto

me

prote

ome

metabolome

Beyond the central dogma

S P

networks

G1 G2

SPF MPFCdk

CycBS

Cdk

CycBM

SPF

MPFCdk

CycBS

Cdk

CycBM

G1 G2

Start

G2/M

exit

cell

division

controlbox

DNA replication

chromosomesegregation

ubiquitindependentproteolysis

reversibleTyrosinephosphorylation

binding of astoichiometricinhibitor

SPF

MPF

cytoplasmic mass doubling time

Cdk

CycBS

Cdk

CycBM

G1 G2

Start

G2/M

exit

0

50

100

150

350

400

WT wee1 - cki -

+ -+ + -

cycl

e t

ime (

min

)

cki –

wee1 -

G1

S

G2

M

cdc25 -

G1

S

G2

M

G1S

G2

M

G1

S

G2

M

G1

S

G2

viability

cytoplasmic mass doubling

time

Balanced growth and division

0

50

100

150

350

400

0

50

100

150

350

400

WT wee1 - cki -

+ -+ + -

cki –

wee1 -

G1

S

G2

M

cdc25 -

G1

S

G2

M

G1S

G2

M

G1

S

G2

M

G1

S

G2

cell

volu

me a

t div

isio

n (

fl)

Balanced growth and divisioncy

cle t

ime (

min

)

viability

G1 G2

SPF

pheromone

-

Cdk

CycBS

Cdk

CycBM

MPF

G1 G2

inhibitor-

SPFCdk

CycBS

Cdk

CycBMStart

MPF

G1 G2

inhibitor-

Start

G2/M

SPFCdk

CycBS

MPFCdk

CycBM

Cdk

CycB

G1 G2

cell mass doubling time

+ +Sta

rt

G2/M

exit

Sta

rtCK

I

Cdk

CycB

CK

I

P

CK

I

AA

Exit

APCM

Cdk

G2/M

P

Cdc25

Wee1Cdk

CycB

APCG1

Cdk

CycB

AA

Cdk

CycB

inactive

Wee1P

inactive

Cdc25

P

inactive

APCM

delay

inactive

APCG1inactive

?

fission yeast budding yeast

Mutants in Fission Yeastgene viability trait

cdc2- no block in G1 and G2cdc13- no endoreplicationrum1- yes sterileste9- yes sterilewee1- yes small cellscdc25- no block in G2

cdc2op yes wtcdc13op yes wtrum1op no endoreplicationste9op no endoreplicationwee1op yes large cellscdc25op yes small cells

wee1- rum1 no extremely smallwee1- cdc25 yes quantized cycleswee1- cdc25op no mitotic catastrophe

0 50 100 1500.0

0.5

1.0

0.0

0.2

0

1

0

1

1

2

period of oscillation= cycle time= mass doubling time (tD)

dm/dt = m where = ln2/tD

rate ~ mass

APCM

Cdk

CycB

APCG1

CK

I

S/G2G1M

time (min)

M

CycB

periodtD

mass (m)

tim

e

0 50 100 1500.0

0.5

1.0

0.0

0.2

0

1

0

1

1

2

period

dm/dt = m where = ln2/tD

APCG1

Cdk

CycB

APCM

CycB

CK

I

S/G2G1M

time (min)

M

mass

Size control over the cell cycleSize control over the cell cycle

rate ~ mass

periodtD

mass (m)

tim

e

Inside view ?

Sta

rtCK

I

Cdk

CycB

CK

I

P

CK

I

AA

Exit

APCM

CdkP

Cdc25

Wee1Cdk

CycB

APCG1

Cdk

CycB

AA

Cdk

CycB

Wee1P

Cdc25

P

APCG1

APCM

delay

cell mass

Cdk/C

ycB

cell mass

Cdk/C

ycB

cell mass

Cdk/C

ycB

G2/M

0 1 2

0.0

0.2

0.4

1.4

1.6 stable s.s.unstable s.s.min/max

Cd

k/C

ycB

G1

S/G2

M

cell mass

Bifurcation diagram of the cell cycle control networkBifurcation diagram of the cell cycle control networkBifurcation diagram of the cell cycle control networkBifurcation diagram of the cell cycle control network

0 1 2

0.0

0.2

0.4

1.4

1.6 stable s.s.unstable s.s.min/max

Cd

k/C

ycB

G1

S/G2

M

cell mass

Cell cycle regulation on the bifurcation diagram Cell cycle regulation on the bifurcation diagram Cell cycle regulation on the bifurcation diagram Cell cycle regulation on the bifurcation diagram

dividingcellnewborn

cellS

tart

G2/M

Exit

G1S/G2

M

0

0.4

0 2 431 5

G1 checkpoint

cell mass

Cdk/C

ycB

G1S/G2

0.4

0

0.8

1.2

1.6

0 2 431 5

M

metaphase checkpoint

cell mass

Cdk/C

ycB

G2

/M

Exit

G1S/G2

M

0

0.4

G2 checkpoint

cell mass

Cdk/C

ycB

0 2 431 5