DNA modifying agents as tools for studying chromatin structure.

Abstract

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.