How Xenopus laevis embryos replicate reliably: investigating the random-completion problem

Abstract

DNA synthesis in \textit{Xenopus} frog embryos initiates stochastically in time at many sites (origins) along the chromosome. Stochastic initiation implies fluctuations in the time to complete and may lead to cell death if replication takes longer than the cell cycle time ($\approx 25$ min). Surprisingly, although the typical replication time is about 20 min, \textit{in vivo} experiments show that replication fails to complete only about 1 in 300 times. How is replication timing accurately controlled despite the stochasticity? Biologists have proposed two solutions to this "random-completion problem." The first solution uses randomly located origins but increases their rate of initiation as S phase proceeds, while the second uses regularly spaced origins. In this paper, we investigate the random-completion problem using a type of model first developed to describe the kinetics of first-order phase transitions. Using methods from the field of extreme-value statistics, we derive the distribution of replication-completion times for a finite genome. We then argue that the biologists' first solution to the problem is not only consistent with experiment but also nearly optimizes the use of replicative proteins. We also show that spatial regularity in origin placement does not alter significantly the distribution of replication times and, thus, is not needed for the control of replication timing.

16 pages, 9 figures, submitted to Physical Review E

References in corpus (4)

• Kinetic model of DNA replication in eukaryotic organisms
• Nucleation and growth in one dimension, part I: The generalized Kolmogorov-Johnson-Mehl-Avrami model
• Nucleation and growth in one dimension, part II: Application to DNA replication kinetics
• How Xenopus laevis replicates DNA reliably even though its origins of replication are located and initiated stochastically

Cited by in corpus (8)

• Stochastic mechano-chemical kinetics of molecular motors: a multidisciplinary enterprise from a physicist's perspective
• Extreme reductions of entropy in an electronic double dot
• Optimal Placement of Origins for DNA Replication
• Cell-to-cell variability and robustness in S-phase duration from genome replication kinetics
• Inferring the spatiotemporal DNA replication program from noisy data
• Cluster-scaling, chaotic order and coherence in DNA
• A chromatin structure based model accurately predicts DNA replication timing in human cells
• Dynamic cluster-scaling in DNA