A model for the spatiotemporal organization of DNA replication in Saccharomyces cerevisiae.
DNA replication in eukaryotes is considered to proceed according to a precise program in which each chromosomal region is duplicated in a defined temporal order. However, recent studies reveal an intrinsic temporal disorder in the replication of yeast chromosome VI. Here we provide a model of the chromosomal duplication to study the temporal sequence of origin activation in budding yeast. The model comprises four parameters that influence the DNA replication system: the lengths of the chromosomes, the explicit chromosomal positions for all replication origins as well as their distinct initiation times and the replication fork migration rate. The designed model is able to reproduce the available experimental data in form of replication profiles. The dynamics of DNA replication was monitored during simulations of wild type and randomly perturbed replication conditions. Severe loss of origin function showed only little influence on the replication dynamics, so systematic deletions of origins (or loss of efficiency) were simulated to provide predictions to be tested experimentally. The simulations provide new insights into the complex system of DNA replication, showing that the system is robust to perturbation, and giving hints about the influence of a possible disordered firing.
Spiesser
T W
TW
Computational Systems Biology, Max Planck Institute for Molecular Genetics, Ihnestrabetae 73, 14195 Berlin, Germany.
Klipp
E
E
Barberis
Matteo
M
D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics; D004271:DNA, Fungal / Q000096:biosynthesis* / Q000235:genetics; D005800:Genes, Fungal; D008954:Models, Biological; D009154:Mutation; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
C076558:CLB5 protein, S cerevisiae; D019926:Cyclin B; D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins