Chemical nucleases as probes for studying DNA-protein interactions.
Chemical nucleases as probes for studying DNA-protein interactions.
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DOI：
10.1042/bj3050345
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发表时间：
1995-01
期刊：
影响因子：
--
通讯作者：
A. Papavassiliou
中科院分区：
文献类型：
--
作者：
A. Papavassiliou
Over the past fifteen years much research has been devoted to the mode(s) by which the linear DNA macromolecule communicates with cellular proteins in the course of genetic programming, thus determining the patterns of growth and development in living organisms. A plethora of proteins have been shown to interact non-covalently with DNA either as structural elements, exemplified by the histones of eukaryotic chromatin, or as components of the complex cellular machineries operating in the essential biological processes of DNA replication, transcription and recombination. DNA-histone interactions are largely sequence neutral and rely mostly on electrostatic attractions between basic amino acids and the negatively charged sugar-phosphate backbone, whereas the DNA binding of proteins necessary for the conservation and selective reading of genetic information (e.g. transcription factors) is highly sequence-dependent. The principal basis for such sequence discrimination is direct contact between the polypeptide chain and the exposed edges of the base pairs, in both the major and minor grooves of B-DNA. These contacts may involve either hydrogen bonding or van der Waals, ionic and hydrophobic interactions between amino acid residues of the protein and specific atoms of the purine and pyrimidine rings of the DNA double helix (for a recent review see [1]). Furthermore, these direct interactions are supplemented by the sequencedependent bendability or deformability of DNA, which limits the energetically favourable configurations ofa particular binding site and thereby imposes additional sequence-dependent constraints on the binding affinity [1]. An emerging feature of specific DNA-protein binding is that several parameters governing DNA structure and conformational microheterogeneity [e.g. deoxyribose conformation and phosphatephosphate distances (groove size)] can be significantly distorted by interacting proteins. Although the ultimate fine molecular description of DNAprotein complexes requires crystallographic and/or n.m.r. analyses, the development and application of a veritable armoury of enzymic and chemical probes that are capable of breaking (either directly or indirectly) the backbone ofDNA has made it possible to obtain quite detailed structural and dynamic pictures of
