0 400 1000

0.0

1.5

Time (min)

P53

tot

0 400 1000

0.00

4

Time (min)

P53

UU

0 400 1000

0.0

1.0

Time (min)

Mdm

2nuc

0 400 1000

0.0

1.5

Time (min)

DN

A d

amag

e

remaining damage

p53

p53 signal generatorp53 signal generator

DNA RepairDNA Repair

remaining damage

p53

p53 signal generator

de novo dNTP supply

initial DNA damage

mutations

dNTP demand+

salvage dNTP supply

- -

excess dNTPdemand

Ciliberto, A., Novak, B. and Tyson, J. J. Steady states and oscillations in the p53/Mdm2 network. Cell Cycle 4, 488-93 (2005).

Lahav, G., et al Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat Genet 36, 147-50 (2004).

-1000 0 1000 2000 3000

05

1015

Time (min)

p53P

-1000 0 1000 2000 3000

02

46

810

Time (min)

m2

-1000 0 1000 2000 3000

02

46

810

Time (min)

Sd

-1000 0 1000 2000 3000

0.0

0.2

0.4

0.6

0.8

1.0

Time (min)

Atm

P

R code implementation

Jarnac Simulation (much faster than R)

Jen KY, Cheung VG: Transcriptional response of lymphoblastoid cells to ionizing radiation. Genome Res 2003, 13:2092-2100.

0 5 10 15 20

0.0

1.0

2.0

hours

MT

HF

D1

3 gray10 gray

0 5 10 15 20

0.0

1.0

2.0

hours

TY

MS

0 5 10 15 20

0.0

1.0

2.0

hours

RR

M1

0 5 10 15 20

0.0

1.0

2.0

hours

RR

M2

0 5 10 15 20

0.0

1.0

2.0

hours

TK

1

0 5 10 15 20

0.0

1.0

2.0

hours

DC

K

0 5 10 15 20

0.0

1.0

2.0

hours

DG

UO

K

0 5 10 15 20

0.0

1.0

2.0

hours

TK

2

0 5 10 15 20

0.0

1.0

2.0

hours

PC

NA

0 5 10 15 20

0.0

1.0

2.0

hours

AP

EX

1

0 5 10 15 200.

01.

02.

0

hours

PO

LB

0 5 10 15 20

0.0

1.0

2.0

hours

FE

N1

0 5 10 15 20

0.0

1.0

2.0

hours

LIG

1

0 5 10 15 20

0.0

1.0

2.0

hours

MLH

1

0 5 10 15 20

0.0

1.0

2.0

hours

MS

H2

0 5 10 15 200.

01.

02.

0hours

XR

CC

5

0 5 10 15 20

02

46

810

hours

MD

M2

0 5 10 15 20

0.0

1.0

2.0

hours

AK

T1

0 5 10 15 20

0.0

1.0

2.0

hours

TP

53

0 5 10 15 20

02

46

810

hours

CD

KN

1A