Self-organization of domain structures by DNA-loop-extruding enzymes.
Self-organization of domain structures by DNA-loop-extruding enzymes.
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DOI：
10.1093/nar/gks925
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发表时间：
2012-12
影响因子：
14.9
通讯作者：
Marko JF
中科院分区：
文献类型：
--
作者：
Alipour E;Marko JF
细胞的长染色体DNA被组织成比单个DNA结合酶大得多的环状结构域，这就提出了如何控制这种结构的形成的问题。我们提出了一个模型，用于生成定义的染色体环，分子机器的基础上，由两个耦合和方向相反的运动元素，从双螺旋沿着，他们易位的挤压循环，而排除彼此空间。如果这些机器不与DNA分离（无限持续合成能力），就会得到一个无序的、指数稳定状态的小循环分布。然而，如果解离和重新绑定的机器发生在一个有限的速率（有限的持续合成能力），稳定状态定性地改变到一个高度有序的“堆叠”的配置与抑制波动，组织一个单一的大，稳定的环域锚定的几个机器。结果域的大小可以简单地通过边界元素来调节，边界元素使挤出机的进程停止。这些类型的分子机器的可能实现进行了讨论，主要集中在染色体复合物的结构维护，并与I型限制性内切酶的讨论。这种机制可以解释真核生物有丝分裂染色体的几何均匀折叠，通过挤压预编程环和伴随的染色体压实。
The long chromosomal DNAs of cells are organized into loop domains much larger in size than individual DNA-binding enzymes, presenting the question of how formation of such structures is controlled. We present a model for generation of defined chromosomal loops, based on molecular machines consisting of two coupled and oppositely directed motile elements which extrude loops from the double helix along which they translocate, while excluding one another sterically. If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained. However, if dissociation and rebinding of the machines occurs at a finite rate (finite processivity), the steady state qualitatively changes to a highly ordered ‘stacked’ configuration with suppressed fluctuations, organizing a single large, stable loop domain anchored by several machines. The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines. Possible realizations of these types of molecular machines are discussed, with a major focus on structural maintenance of chromosome complexes and also with discussion of type I restriction enzymes. This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.