Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

TY - JOUR

T1 - Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

AU - Goldar, A.

AU - Arneodo, A.

AU - Audit, B.

AU - Argoul, F.

AU - Rappailles, A.

AU - Guilbaud, Guillaume

AU - Petryk, N.

AU - Kahli, M.

AU - Hyrien, O.

PY - 2016

Y1 - 2016

N2 - We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin's fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.

AB - We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin's fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.

U2 - 10.1038/srep22469

DO - 10.1038/srep22469

M3 - Journal article

AN - SCOPUS:84960156863

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 22469

ER -