A Bulky DNA Lesion Derived from a Highly Potent Polycyclic Aromatic Tumorigen Stabilizes Nucleosome Core Particle Structure
A Bulky DNA Lesion Derived from a Highly Potent Polycyclic Aromatic Tumorigen Stabilizes Nucleosome Core Particle Structure
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DOI：
10.1021/bi101560y
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发表时间：
2010-11-23
期刊：
影响因子：
2.9
通讯作者：
Broyde, Suse
中科院分区：
文献类型：
--
作者：
Cai, Yuqin;Wang, Lihua;Broyde, Suse
利用65 ns分子动力学模拟研究了大体积DNA损伤对核小体核心颗粒（NCP）结构和动力学的影响，该核小体核心颗粒含有一种异常有效的肿瘤致癌物二苯并[a， 1]芘，它可以抵抗游离DNA中的核苷酸切除修复（NER）。我们的研究结果表明，相对于未修饰的NCP，病变通过堆叠相互作用、改进的沃森-克里克碱基配对、DNA和组蛋白之间的氢键以及阻尼动力学来稳定核小体。这些发现表明，这些病变在核小体环境中应该像在游离DNA中一样对NER具有抗性。
The impact of a bulky DNA lesion on the structure and dynamics of a nucleosome core particle (NCP) containing a lesion derived from the unusually potent tumorigen dibenzo[a,l]pyrene that resists nucleotide excision repair (NER) in free DNA was investigated using 65 ns molecular dynamics simulations. Our results reveal that, relative to unmodified NCP, the lesion stabilizes the nucleosome via stacking interactions, improved Watson-Crick base pairing, hydrogen bonding between DNA and histones, and damped dynamics. These findings suggest that such lesions should be as resistant to NER in the nucleosome environment as they are in free DNA.