Millard J T
Department of Chemistry, Colby College, Waterville, Maine 04901, USA.
Biochimie. 1996;78(10):803-16. doi: 10.1016/s0300-9084(97)84332-5.
DNA modification leads to mutagenicity, carcinogenicity, and cytotoxicity. Because the majority of cellular DNA exists as chromatin, histone and other proteins may mediate DNA binding and bonding reactions in vivo. Chromatin modification by a wide variety of agents, including intercalators, groove binders, cross-linkers, and strand cleavers, is reviewed. Although the majority of agents demonstrate a preference for linker over core DNA, the sequence preference appears to be retained in most cases, suggesting that both the major and minor grooves in chromatin are quite accessible to small molecules. Furthermore, only a handful of agents demonstrate the 10-11 base pair periodicity of hydroxyl radical, strongly supporting a dynamic model of nucleosome structure.
DNA修饰会导致致突变性、致癌性和细胞毒性。由于大多数细胞DNA以染色质的形式存在,组蛋白和其他蛋白质可能在体内介导DNA的结合和键合反应。本文综述了包括嵌入剂、沟槽结合剂、交联剂和链切割剂在内的多种试剂对染色质的修饰作用。尽管大多数试剂对连接区DNA的偏好高于核心DNA,但在大多数情况下序列偏好似乎得以保留,这表明染色质中的大沟和小沟对小分子来说都是相当容易接近的。此外,只有少数试剂表现出羟基自由基的10 - 11碱基对周期性,这有力地支持了核小体结构的动态模型。