Title
3D replicon distributions arise from stochastic initiation and domino-like DNA replication progression
Date Issued
07 April 2016
Access level
open access
Resource Type
journal article
Author(s)
Technische Universität Darmstadt
Publisher(s)
Nature Publishing Group
Springer Nature
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.
Volume
7
Language
English
OCDE Knowledge area
Genética, Herencia
Scopus EID
2-s2.0-84963660265
PubMed ID
Source
Nature Communications
ISSN of the container
2041-1723
Sources of information:
Directorio de Producción Científica
Scopus