0 400 1000 0.0 1.5 Tim e (m in) P53tot 0 400 1000 0.004 Tim e (m in) P 53U U 0 400 1000 0.0 1.0 Tim e (m in) M dm 2nuc 0 400 1000 0.0 1.5 Tim e (m in) DNA dam age remaining dam age p53 p53 signal generator p53 signal generator D N A R epair D N A R epair remaining dam age p53 p53 signal generator de novo dN TP supply initial D N A dam age mutations dN TP dem and + salvage dN TP supply - - excess dN TP dem and 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).
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). R code implementation. - PowerPoint PPT Presentation
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Transcript
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.