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Table 3 Comparison of model outcomes with experiments for different perturbations.

From: Modelling the onset of senescence at the G1/S cell cycle checkpoint

Loss-Of-Function (LoF)

Gene

Model outcome

Experimental outcome

Comparison with experiments whose protocol include DNA damage

p38MAPK

Loss of senescence and of apoptosis

Reduced apoptosis [35]

CHEK2

Loss of senescence

Loss of senescence [37]

ATM

Loss of senescence and of apoptosis

Reduced apoptosis [41]

Comparison with experiments whose protocol does not include DNA damage

CHEK1

No damage: proliferation

With damage: loss of senescence

Apoptosis enhanced [42]

p14ARF

No damage: proliferation

With damage: senescence enhanced & loss of apoptosis

?

Mdm2

No damage: proliferation

With damage: apoptosis

Apoptosis [45]

p16INK4a

No damage: proliferation

With damage: loss of senescence

Loss of senescence

[6, 7, 21]

p21

No damage: proliferation

With damage: loss of senescence

Proliferation [47]

p53

No damage: proliferation

With damage: loss of senescence & apoptosis

Proliferation & loss of senescence [48]

ATR

No damage: proliferation

With damage: senescence enhanced & loss of apoptosis

?

CDC25A

No damage: loss of proliferation

With damage: senescence enhanced

?

RB1

No damage: proliferation

With damage: apoptosis

Apoptosis enhanced [50]

E2F

No damage: loss of proliferation

With damage: similar to the wild type

Loss of proliferation [51]

p53 & Mdm2

No damage: proliferation

With damage: loss of senescence & apoptosis

Proliferation [45]

Gain-Of-Function (GoF)

Gene

Model outcome

Experimental outcome

Comparison with experiments whose protocol include DNA damage

CHEK2

Senescence enhanced

Apoptosis & senescence [39, 40]

Mdm2

Senescence enhanced & loss of apoptosis

Loss of apoptosis [46]

p21

Similar to the wild type

Loss of proliferation or senescence [43]

Comparison with experiments whose protocol does not include DNA damage

p38MAPK

No damage: [1, 2] loss of proliferation; [3] apoptosis

With damage: [1, 2] senescence enhanced & loss of apoptosis; [3] apoptosis

Senescence [36]

CHEK1

No damage: loss of proliferation

With damage: similar to the wild type

?

p14ARF

No damage: proliferation

With damage: apoptosis

Apoptosis [43]

p16INK4a

No damage: cell cycle arrest with probability ~ 0.9

With damage: [1, 2] similar to the wild type; [2] senescence enhanced

Proliferation decreased or senescence [6, 7, 21]

p53

No damage: [1, 2] loss of proliferation; [2] apoptosis

With damage: [1] senescence enhanced & loss of apoptosis; [2]: apoptosis

Apoptosis [4, 48]

ATM

No damage: [1] loss of proliferation; [2] senescence

With damage: [1] loss of senescence & apoptosis; [2] senescence enhanced

?

ATR

No damage: [1, 2] loss of proliferation

With damage: [1] senescence enhanced & loss of apoptosis; [2] loss of senescence & apoptosis enhanced

Senescence [32]

CDC25A

No damage: [1, 2] proliferation

With damage: [1, 2] loss of senescence

Proliferation [49]

RB1

No damage: loss of proliferation

With damage: similar to the wild type

Cycle arrest [48]

E2F

No damage: proliferation

With damage: apoptosis

Apoptosis [51]

  1. Distinction is made between experiments that include DNA damage or not (see Supplementary material). Question marks indicate cases for which no data were found.