Abstract：
In nature, DNA exists primarily in a highly compacted form. The compaction of DNA in vivo is mediated by cationic proteins: histones in somatic nuclei and protamines in sperm chromatin. The extreme, nearly crystalline packaging of DNA by protamines in spermatozoa is thought to be essential for both efficient genetic delivery as well as DNA protection against damage by mutagens and oxidative species. The protective role of protamines is required in sperm, as they are sensitive to ROS damage due to the progressive loss of DNA repair mechanisms during maturation. The degree to which DNA packaging directly relates to DNA protection in the condensed state, however, is poorly understood. Here, we utilized different polycation condensing agents to achieve varying DNA packaging densities and quantify DNA damage by free radical oxidation within the condensates. Although we see that tighter DNA packaging generally leads to better protection, the length of the polycation also plays a significant role. Molecular dynamics simulations suggest that longer polyarginine chains offer increased protection by occupying more space on the DNA surface and forming more stable interactions. Taken together, our results suggest a complex interplay among polycation properties, DNA packaging density, and DNA protection against free radical damage within condensed states.
摘要：
在大自然中,DNA主要以高度压缩的形式存在。体内DNA的压缩是由阳离子蛋白介导的：体细胞核中的组蛋白和精子染色质中的鱼精蛋白。极端的,精子中鱼精蛋白对DNA的几乎结晶包装被认为对于有效的遗传传递以及DNA保护免受诱变剂和氧化物质的损害至关重要。精子中需要鱼精蛋白的保护作用，由于成熟过程中DNA修复机制的逐渐丧失，它们对ROS损伤敏感。DNA包装与DNA在凝聚状态下的保护直接相关的程度，然而,知之甚少。这里,我们利用不同的聚阳离子缩合剂来实现不同的DNA包装密度，并量化冷凝物中自由基氧化对DNA的损伤。虽然我们看到更紧密的DNA包装通常会导致更好的保护，聚阳离子的长度也起着重要的作用。分子动力学模拟表明，较长的聚精氨酸链通过在DNA表面占据更多空间并形成更稳定的相互作用来提供增强的保护。一起来看,我们的结果表明，聚阳离子性质之间存在复杂的相互作用，DNA包装密度,和DNA保护免受凝聚状态下的自由基损伤。
