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3D replicon distributions arise from stochastic initiation and domino-like DNA replication progression.

Löb, D. and Lengert, N. and Chagin, V. O. and Reinhart, M. and Casas-Delucchi, C. S. and Cardoso, M. Cristina and Drossel, B. (2016):
3D replicon distributions arise from stochastic initiation and domino-like DNA replication progression.
In: Nature communications, p. 11207, 7, ISSN 2041-1723, [Article]

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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.

Item Type: Article
Erschienen: 2016
Creators: Löb, D. and Lengert, N. and Chagin, V. O. and Reinhart, M. and Casas-Delucchi, C. S. and Cardoso, M. Cristina and Drossel, B.
Title: 3D replicon distributions arise from stochastic initiation and domino-like DNA replication progression.
Language: English
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.

Journal or Publication Title: Nature communications
Volume: 7
Divisions: 10 Department of Biology
10 Department of Biology > Cell Biology and Epigenetics
05 Department of Physics > Institute for condensed matter physics > Statistische Physik und komplexe Systeme
05 Department of Physics > Institute for condensed matter physics
05 Department of Physics
Date Deposited: 02 Nov 2016 14:43
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