Modeling inhomogeneous DNA replication kinetics.
Modeling inhomogeneous DNA replication kinetics.
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DOI：
10.1371/journal.pone.0032053
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bechhoefer J
中科院分区：
文献类型：
--
作者：
Gauthier MG;Norio P;Bechhoefer J
在真核生物中，DNA复制起始于一系列称为起点的染色体位置，其中复制叉组装成双向进行基因组复制。这些起点的分布和发射率，以及分叉前进的速度，决定了复制过程的程序。以前在真核生物中模拟DNA复制的尝试集中在复制叉的发射率和速度在整个基因组中是均匀的或统一的情况下。然而，现在已知沿着基因组的起源活动存在很大的变化，并且分叉速度也可能发生变化。在这里，我们概括了以前的方法来建模复制，允许任意空间变化的起始速率和叉速度。我们推导出率方程的左，右移动的叉子和复制概率随时间的推移，可以数值求解，以获得平均场复制程序。该方法准确地再现了DNA复制模拟的结果。我们还成功地调整了我们的方法，以逆问题的拟合测量单DNA分子上进行的DNA复制。由于这种测量是在基因组的特定部分上进行的，所检测的DNA分子可能被来自所研究的分子内部或外部的叉复制，这个问题通过使用模型边界处的传入复制叉的有效通量来表示所研究区域之外的起源活动来解决。使用这种方法，我们表明，可靠的推论，可以作出关于基因组的特定部分的复制，即使可以从单分子实验中获得的数据量通常是有限的。
In eukaryotic organisms, DNA replication is initiated at a series of chromosomal locations called origins, where replication forks are assembled proceeding bidirectionally to replicate the genome. The distribution and firing rate of these origins, in conjunction with the velocity at which forks progress, dictate the program of the replication process. Previous attempts at modeling DNA replication in eukaryotes have focused on cases where the firing rate and the velocity of replication forks are homogeneous, or uniform, across the genome. However, it is now known that there are large variations in origin activity along the genome and variations in fork velocities can also take place. Here, we generalize previous approaches to modeling replication, to allow for arbitrary spatial variation of initiation rates and fork velocities. We derive rate equations for left- and right-moving forks and for replication probability over time that can be solved numerically to obtain the mean-field replication program. This method accurately reproduces the results of DNA replication simulation. We also successfully adapted our approach to the inverse problem of fitting measurements of DNA replication performed on single DNA molecules. Since such measurements are performed on specified portion of the genome, the examined DNA molecules may be replicated by forks that originate either within the studied molecule or outside of it. This problem was solved by using an effective flux of incoming replication forks at the model boundaries to represent the origin activity outside the studied region. Using this approach, we show that reliable inferences can be made about the replication of specific portions of the genome even if the amount of data that can be obtained from single-molecule experiments is generally limited.
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影响因子：
21.3
作者：
Feng, Wenyi;Collingwood, David;Boeck, Max E;Fox, Lindsay A;Alvino, Gina M;Fangman, Walton L;Raghuraman, Mosur K;Brewer, Bonita J
通讯作者：
Brewer, Bonita J
影响因子：
3.7
作者：
Goldar, Arach;Labit, Helene;Hyrien, Olivier
通讯作者：
Hyrien, Olivier
影响因子：
1.8
作者：
FRANK, FC
通讯作者：
FRANK, FC
影响因子：
2.4
作者：
Jun, S;Bechhoefer, J
通讯作者：
Bechhoefer, J
DOI：
10.1073/pnas.0809350106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Katsuno, Yuko;Suzuki, Ayumi;Nakanishi, Makoto
通讯作者：
Nakanishi, Makoto