Modeling the heterogeneity of p53 dynamics in DNA damage response.
The tumor suppressor p53 can be activated by DNA damage and exhibits undamped pulses. Recent reports have demonstrated a non-threshold mechanism for p53 dynamics. However, no related theoretical studies have been proposed. Here, we constructed a refined DNA damage repair model that incorporated both intrinsic and extrinsic DNA lesions. We proposed that the basal DNA damage may trigger significant fractions of p53 pulses. We also reproduced the heterogeneity of p53 dynamics in experiments. The number of p53 pulses showed no correlations with DNA damage. We also replicated the linear correlation between DNA damage and the probability of igniting a pulse. Our model has unraveled the heterogeneous p53 responses.
* Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, Jiangsu 210008, P. R. China.
Wenlei
W
Wu
* Institute and Hospital of Stomatology, Nanjing University Medical School, Nanjing, Jiangsu 210008, P. R. China.
Weibin
W
Sun
† School of Life Sciences, AnQing Normal University, AnQing, Anhui 246011, P. R. China.
Tingzhe
T
Sun
D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D004260:DNA Repair / Q000502:physiology*; D005720:Gamma Rays; D008954:Models, Biological; D008962:Models, Theoretical; D009010:Monte Carlo Method; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D013269:Stochastic Processes; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2
DNA damage repair; heterogeneity; linear response; p53 pulse