原创力文档a dynamic stochastic model for dna replication initiation in early embryosdna复制起始的动态随机模型在早期胚胎.pdfVIP
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a dynamic stochastic model for dna replication initiation in early embryosdna复制起始的动态随机模型在早期胚胎
A Dynamic Stochastic Model for DNA Replication
Initiation in Early Embryos
1 ´ ` 2¤ 2 2
Arach Goldar *, Helene Labit , Kathrin Marheineke , Olivier Hyrien *
´
´ ´ ´ ´ ` ´
1 Service de Biologie Integrative et de Genetique Moleculaire, Commissariat a l’Energie Atomique, Gif-sur-Yvette, France, 2 Ecole Normale Superieure, CNRS UMR 8541,
Paris, France
Abstract
Background: Eukaryotic cells seem unable to monitor replication completion during normal S phase, yet must ensure a
reliable replication completion time. This is an acute problem in early Xenopus embryos since DNA replication origins are
located and activated stochastically, leading to the random completion problem. DNA combing, kinetic modelling and
other studies using Xenopus egg extracts have suggested that potential origins are much more abundant than actual
initiation events and that the time-dependent rate of initiation, I(t), markedly increases through S phase to ensure the rapid
completion of unreplicated gaps and a narrow distribution of completion times. However, the molecular mechanism that
underlies this increase has remained obscure.
Methodology/Principal Findings: Using both previous and novel DNA combing data we have confirmed that I(t) increases
through S phase but have also established that it progressively decreases before the end of S phase. To explore plausible
biochemical scenarios that might explain these features, we have performed comparisons between numerical simulations
and DNA combing data. Several simple models we
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