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Molecular Mechanism of Spontaneous Nucleosome Unraveling

机译:自发性核小孔解开的分子机制

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Meters of DNA wrap around histone proteins to form nucleosomes and fit inside the micron-diameter nucleus. For the genetic information encoded in the DNA to become available for transcription, replication, and repair, the DNA-histone assembly must be disrupted. Experiment has indicated that the outer stretches of nucleosomal DNA "breathe" by spontaneously detaching from and reattaching to the histone core. Here, we report direct observation of spontaneous DNA breathing in atomistic molecular dynamics simulations, detailing a microscopic mechanism of the DNA breathing process. According to our simulations, the outer stretches of nucleosomal DNA detach in discrete steps involving 5 or 10 base pairs, with the detachment process being orchestrated by the motion of several conserved histone residues. The inner stretches of nucleosomal DNA are found to be more stably associated with the histone core by more abundant nonspecific DNA-protein contacts, providing a microscopic interpretation of nucleosome unraveling experiments. The CG content of nucleosomal DNA is found to anticorrelate with the extent of unwrapping, supporting the possibility that AT-rich segments may signal the start of transcription by forming less stable nucleosomes. (C) 2018 Elsevier Ltd. All rights reserved.
机译:DNA米缠绕组蛋白蛋白质以形成核体并配合在微米直径核内。对于在DNA中编码的遗传信息,以可用于转录,复制和修复,必须破坏DNA-组合组件。实验表明,通过自发地脱离并重新连接到组蛋白核心并重新连接的核致组DNA“呼吸”的外延。在这里,我们报告了对原子分子动力学模拟中的自发DNA呼吸的直接观察,详细说明了DNA呼吸过程的显微镜机制。根据我们的模拟中,核小体DNA的分离在涉及5或10个碱基对不连续的步骤外延伸,与所述分离过程由几个保守组蛋白残基的运动协调。发现核体DNA的内延伸通过更丰富的非特异性DNA蛋白触点与组蛋白核心更稳定地相关,提供了对核小体解开实验的微观解释。核小体DNA的CG含量被发现与展开的程度anticorrelate,支持了富含AT的段可以通过形成不太稳定的核信号转录起始的可能性。 (c)2018年elestvier有限公司保留所有权利。

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