This volume contains the texts of the nineteen lectures presented at the NATO-ASI - FEBS Course on "DNA - ligand interactions: from drugs to proteins." The Advanced Study Institute (ASIl was held from August 30th to September 11th. 1986 in the Abbey of Fontevraud (France). The ASI was attended by 112 participants from a wide scientific horizon and from twentyone different countries. It was in some way a follow-up of the ASI held in Maratea. Italy in May 1981 and which was published in the NATO ASI Life Science series as volume 45. While much has been learned about the way the cellular machinery maintains and transmits the genetic heritage. as well as how these processes are regulated. little is Known about how the interactions between the various partners involved are taKing place. The interactions of drugs and proteins with nucleic acids are of evident importance in the understanding of these problems. The spectacular advances in recombinant DNA technology and the increased sophistication of biophysical techniques. in particular >:-ray diffraction and nuclear magnetic resonance. have created a scientific environment which is highly promising for the future of research in molecular biology. These advances permH the serious hope that biology on the molecular level may become a r-eality. Some of the contributions at the ASI presented the most recent advances in this e>:citing field.
Table of ContentsA) DNA Structure and Interaction with Small Molecules.- DNA structure: Current results from single crystal x-ray diffraction studies.- One- and two- dimensional NMR studies of the structures of simple sequence DNAs.- The major and minor grooves of the DNA helix as conduits for information transfer.- Unusual DNA structures and gene regulation.- Specificity and dynamics of protein nucleic acid interactions.- DNA and its counterions: metal ions, amino acids, histones and protamines.- Dynamic aspects of antibiotic DNA interaction.- Specific gene regulation of oligodeoxynucleotides covalently linked to intercalating agents.- Pharmacology of DNA binding drugs.- B) DNA Protein Interactions: Repressor Operator Systems.- On the nature and specificity of DNA-protein interactions in the regulation of gene expression.- Searching for the code of ideal protein-DNA recognition.- trp Repressor, a crystallographic study of allostery in genetic regulation.- Structural studies of three DNA binding proteins: catabolite gene activator protein, resolvase and the Klenow fragment of DNA polymerase I.- A two-dimensional NMR study of the complex of lac repressor headpiece with a 14 base pair lac operator fragment.- C) DNA Protein Interactions: Methylation and Restriction Enzymes..- DNA methylation and mismatch repair: molecular specificities.- Recognition of DNA sequences by restriction endonucleases.- Mechanism and specificity of two restriction enzymes, CauI and CauII, that recognize asymmetrical DNA sequences.- Structure of the DNA-EcoRI endonuclease recognition complex.- D) Outlook: DNA-Protein Interactions of Complex Systems.- Antibodies to nucleic acids.- Summary and Conclusions.- Research Seminars.- Posters.- Participants.