title: 3D replicon distributions arise from stochastic initiation and domino-like DNA replication progression.
abstract: DNA replication dynamics in cells from higher eukaryotes follows very complex but highly efficient mechanisms. However, the principles behind initiation of potential replication origins and emergence of typical patterns of nuclear replication sites remain unclear. Here, we propose a comprehensive model of DNA replication in human cells that is based on stochastic, proximity-induced replication initiation. Critical model features are: spontaneous stochastic firing of individual origins in euchromatin and facultative heterochromatin, inhibition of firing at distances below the size of chromatin loops and a domino-like effect by which replication forks induce firing of nearby origins. The model reproduces the empirical temporal and chromatin-related properties of DNA replication in human cells. We advance the one-dimensional DNA replication model to a spatial model by taking into account chromatin folding in the nucleus, and we are able to reproduce the spatial and temporal characteristics of the replication foci distribution throughout S-phase.
authors.affiliation: Department of Physics, Institute for Condensed Matter Physics, Technische Universität Darmstadt, 64289 Darmstadt, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Löb
authors.affiliation: Department of Physics, Institute for Condensed Matter Physics, Technische Universität Darmstadt, 64289 Darmstadt, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Lengert
authors.affiliation: Laboratory of Chromosome Stability, Institute of Cytology, St Petersburg 194064, Russia.|Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany.
authors.forename: V O
authors.initials: VO
authors.lastname: Chagin
authors.affiliation: Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany.
authors.forename: M
authors.identifier: http://orcid.org/0000-0003-2340-2478
authors.initials: M
authors.lastname: Reinhart
authors.affiliation: Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany.
authors.forename: C S
authors.initials: CS
authors.lastname: Casas-Delucchi
authors.affiliation: Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Cardoso
authors.affiliation: Department of Physics, Institute for Condensed Matter Physics, Technische Universität Darmstadt, 64289 Darmstadt, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Drossel
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication; D022041:Euchromatin / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006570:Heterochromatin / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D008968:Molecular Conformation; D012093:Replicon; D016196:S Phase / Q000235:genetics; D013269:Stochastic Processes
chemical_list: D022041:Euchromatin; D006570:Heterochromatin; D004247:DNA