Fig 1.
Replication timing from Beacon Calculus simulations.
(a) Diagram of ongoing DNA replication in the same chromosome segment of three different cells. Replication can begin from four discrete locations (origins of replication). Each cell successfully replicates its DNA despite having different patterns of origin activation. (b) DNA replication model written in the Beacon Calculus. (c) Curves showing the mean time at which each position on S. cerevisiae chromosome II was replicated, taken from the Beacon Calculus model where each origin has a licensing probability and firing time from [24] (blue), the Beacon Calculus model where all origins are licensed and have the same firing rate of 0.015 (red), and experimental data from [25] (grey). The Beacon Calculus results are averaged over 500 simulations and shaded regions show the standard error of the mean. The system line has been truncated for clarity (see S1 Text).
Fig 2.
DNA damage from Beacon Calculus simulations.
(a) Cells undergo DNA damage (red) and may carry it forward for generations before an Ada molecule (blue) is generated to repair it. Ada is methylated (gold) as it repairs DNA damage creating a positive feedback loop whereby methylated Ada upregulates transcription of the ada gene. Ada levels are reduced through successive cell divisions. (b) DNA damage model written in the Beacon Calculus. (c-d) Average total Ada and meAda per cell over time. Each trace corresponds to a simulation of a growing population of cells for (c) low DNA damage (kdmg = 0.0001) and (d) high DNA damage (kdmg = 0.01). In each of panels (c-d), 25 simulations are shown. Values for k_basal and k_division are from [26] while k_me is from [30]. Values for k_dmg and kMax were approximated based on the results in [31].
Fig 3.
T-cell antigen receptor ultrasensitivity from Beacon Calculus simulations.
(a) An enzyme enters the proximity of a receptor, binds to the receptor, and phosphorylates the receptor if the enzyme is a kinase or dephosphorylates the receptor if the enzyme is a phosphatase. (b) T-cell antigen receptor model written in the Beacon Calculus with parameters taken from [36]. (c) The fraction of phosphorylated receptors is ultrasensitive to the relative concentration of kinase and phosphatase when the enzyme dwells after modifying a receptor (green) but loses ultrasensitivity if the dwell is removed (blue). Points (shown with standard deviation) are the average of 50 simulations taken after the system reaches a steady state.
Fig 4.
Extensions to the DNA replication model.
The DNA replication model in Fig 1b is modified to include either (a) cooperative origin firing or (b) fork progression through a replication fork barrier. All changes to the model in Fig 1b are highlighted in blue. (c) Results from Fig 1b compared with the simulated models from (a) and (b) where each curve is the average over 500 simulations. Shading shows the standard error of the mean. The system line has been truncated for clarity (see S1 Text). The stall rate sr was chosen to be on average ten times slower than it takes a fork to move 1 kb.