Amitai A, Holcman D
Department of Chemical Engineering and Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge 02139, Massachusetts, USA.
Group of Applied Mathematics and Computational Biology, Ecole Normale Supérieure, 75005 Paris, France.
Phys Rev E. 2018 Mar;97(3-1):032417. doi: 10.1103/PhysRevE.97.032417.
The time for a DNA sequence to find its homologous counterpart depends on a long random search inside the cell nucleus. Using polymer models, we compute here the mean first encounter time (MFET) between two sites located on two different polymer chains and confined locally by potential wells. We find that reducing tethering forces acting on the polymers results in local decondensation, and numerical simulations of the polymer model show that these changes are associated with a reduction of the MFET by several orders of magnitude. We derive here new asymptotic formula for the MFET, confirmed by Brownian simulations. We conclude from the present modeling approach that the fast search for homology is mediated by a local chromatin decondensation due to the release of multiple chromatin tethering forces. The present scenario could explain how the homologous recombination pathway for double-stranded DNA repair is controlled by its random search step.
一段DNA序列找到其同源对应序列所需的时间取决于在细胞核内进行的长时间随机搜索。我们使用聚合物模型计算了位于两条不同聚合物链上且局部受势阱限制的两个位点之间的平均首次相遇时间(MFET)。我们发现,作用于聚合物的束缚力减小会导致局部解聚,聚合物模型的数值模拟表明,这些变化与MFET降低几个数量级有关。我们在此推导出了MFET的新渐近公式,并通过布朗模拟得到了证实。我们从当前的建模方法得出结论,同源性的快速搜索是由多种染色质束缚力的释放导致的局部染色质解聚介导的。目前的情况可以解释双链DNA修复的同源重组途径是如何由其随机搜索步骤控制的。