期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep22469
关键词
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资金
- ANR REFOPOL
- PSL* Research University [ANR-10-LABX-54 MEMO LIFE ANR-11-IDEX-0001-02]
- [ANR10 BLANC1615]
- [EDFV4_104.Rev]
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.
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