Molecular Mechanism of Spontaneous Nucleosome Unraveling.
Molecular Mechanism of Spontaneous Nucleosome Unraveling.
复制标题
自发核小体解开的分子机制。
DOI：
10.1016/j.jmb.2018.11.013
复制
发表时间：
2019
影响因子：
5.6
通讯作者：
Aksimentiev,Aleksei
中科院分区：
文献类型：
--
作者：
Winogradoff,David;Aksimentiev,Aleksei
数米长的DNA包裹在组蛋白周围形成核小体，并装入微米直径的细胞核内。为了使DNA中编码的遗传信息可用于转录、复制和修复，DNA-组蛋白组装必须被破坏。实验表明，核小体DNA的外部延伸通过自发地与组蛋白核心分离和重新附着来“呼吸”。在这里，我们报告直接观察自发DNA呼吸原子分子动力学模拟，详细介绍了DNA呼吸过程的微观机制。根据我们的模拟，核小体DNA的外部延伸在涉及5或10个碱基对的离散步骤中分离，分离过程由几个保守的组蛋白残基的运动协调。核小体DNA的内部延伸被发现更稳定地与组蛋白核心更丰富的非特异性DNA-蛋白质接触，提供了一个核小体解开实验的微观解释。CG含量的核小体DNA被发现与解包的程度，支持的可能性，AT丰富的片段可能通过形成不太稳定的核小体的信号开始转录。
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.
登录
查看更多内容
DOI：
10.1039/c7cp08185e
发表时间：
2018-03-28
期刊：
Physical chemistry chemical physics : PCCP
影响因子：
--
作者：
Yoo J;Aksimentiev A
通讯作者：
Aksimentiev A
DOI：
10.1073/pnas.0500189102
发表时间：
2005-03-01
影响因子：
11.1
作者：
Tomschik, M;Zheng, HC;Leuba, SH
通讯作者：
Leuba, SH
DNA 结合蛋白入侵核小体的动力学。
影响因子：
5.6
作者：
Tims,HannahS;Gurunathan,Kaushik;Levitus,Marcia;Widom,Jonathan
通讯作者：
Widom,Jonathan
DOI：
10.1073/pnas.1613607113
发表时间：
2016-10-25
影响因子：
11.1
作者：
Di Pierro, Michele;Zhang, Bin;Onuchic, Jose N.
通讯作者：
Onuchic, Jose N.
影响因子：
3.7
作者：
Kono H;Shirayama K;Arimura Y;Tachiwana H;Kurumizaka H
通讯作者：
Kurumizaka H