How Xenopus Laevis Replicates DNA Reliably even though Its Origins of Replication are Located and Initiated Stochastically

DNA replication in Xenopus laevis is extremely reliable, failing to complete before cell division no more than once in 10 000 times; yet replication origin sites are located and initiated stochastically. Using a model based on 1D theories of nucleation and growth and using concepts from extreme-value statistics, we derive the distribution of replication times given a particular initiation function. We show that the experimentally observed initiation strategy for Xenopus laevis meets the reliability constraint and is close to the one that requires the fewest resources of a cell.

Figure 1

Schematic of DNA replication model. Space-time diagram showing multiple origins (filled circles), each expanding symmetrically at constant velocity. Domains coalesce when they meet (open circles).

Figure 2

Replication-time distribution function, fixing the mode to be $t^{*}=38$ minutes. Markers are results from Monte Carlo simulations (3000 trials per simulation); solid lines are fits to the Gumbel distribution.

Figure 3

Replication-times distribution function, fixing the mortality rate at $t^{**}=25$ minutes to be ${10}^{-4}$. (The area to the right of the dashed line of each probability distribution function is ${10}^{-4}$.) Markers are results from Monte Carlo simulations (20 000 trials per simulation); solid lines are fits to the Gumbel distribution.

Figure 4

Maximum required fork density, for different replication schemes.