Mathematical modelling of eukaryotic DNA replication
Mathematical modelling of eukaryotic DNA replication
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DOI：
10.1007/s10577-009-9092-4
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发表时间：
2010-01-01
影响因子：
2.6
通讯作者：
Goldar, Arach
中科院分区：
文献类型：
--
作者：
Hyrien, Olivier;Goldar, Arach
真核DNA复制是一个复杂的过程。复制开始于在S期的不同时间激活的数千个起点，并在聚合复制叉相遇时终止。在给定的S相内，潜在的起源比实际的火要丰富得多。复制起点的选择和它们的激活时间在任何两个细胞中都不完全相同。不同的起源表现出不同的效率和不同的发射时间概率分布，赋予随机性的DNA复制过程。高通量微阵列和测序技术提供了越来越庞大的数据集的人口平均时空模式的DNA复制在几个生物体。另一方面，单分子复制映射技术，如DNA梳理，提供了独特的信息，细胞间的DNA复制模式的变异性。需要数学建模来充分理解染色体复制过程的复杂性并正确解释这些数据。数学分析和计算机模拟最近已被用来模拟和解释在酵母酿酒酵母和裂殖酵母粟酒裂殖酵母，在非洲爪蟾卵提取物和哺乳动物细胞的全基因组复制数据。这些工作揭示了起源使用的随机性如何赋予DNA复制过程的鲁棒性和可靠性。
Eukaryotic DNA replication is a complex process. Replication starts at thousand origins that are activated at different times in S phase and terminates when converging replication forks meet. Potential origins are much more abundant than actually fire within a given S phase. The choice of replication origins and their time of activation is never exactly the same in any two cells. Individual origins show different efficiencies and different firing time probability distributions, conferring stochasticity to the DNA replication process. High-throughput microarray and sequencing techniques are providing increasingly huge datasets on the population-averaged spatiotemporal patterns of DNA replication in several organisms. On the other hand, single-molecule replication mapping techniques such as DNA combing provide unique information about cell-to-cell variability in DNA replication patterns. Mathematical modelling is required to fully comprehend the complexity of the chromosome replication process and to correctly interpret these data. Mathematical analysis and computer simulations have been recently used to model and interpret genome-wide replication data in the yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe, in Xenopus egg extracts and in mammalian cells. These works reveal how stochasticity in origin usage confers robustness and reliability to the DNA replication process.