HENRY M. SOBELL

APPENDIX B - Letter for first discussion

DNA (deoxyribonucleic acid) is a helical polymer that contains two polynucleotide chains wrapped around each other and held together by adenine-thymine (A-T) and guanine-cytosine (G-C) hydrogen bonds. Both chains consist of deoxyribose sugar residues chemically linked to a purine or pyrimidine (A, G, T, C) at the C1’ carbon atoms, and by a phosphate through neighboring 3’ and 5’ hydroxyl- oxygen atoms. These chains lie in opposite orientations, being related by pseudo 2-fold symmetry axes located at the level of each base pair and also between adjacent base pairs, perpendicular to the helix axis.

The isomorphous nature of A-T (or T-A) and G-C (or C-G) base pairs allows DNA to carry an irregular sequence while maintaining a perfectly regular helical structure. Since it is the nucleotide base sequence in the gene that carries the information that determines the three-dimensional structure of its gene product (the gene product being, for example -- a protein molecule, a transfer RNA molecule or one of many ribosomal RNA molecules found within the ribosome), this remains as one of the most beautiful concepts provided by the DNA double helix.

But what determines the presence of nuclease hypersensitive sites, observed experimentally with DNA molecules free in solution? And, more to the point, why does 1, 10-phenanthroline copper (I) -- a known intercalator -- mimic the cutting pattern produced by the micrococcal nuclease enzyme in this same study?

[Note: An intercalator is a planar drug or dye molecule (about the size of a base pair) that “slips between” adjacent base pairs. The process can be thought of as being analogous to a dime “slipping between” adjacent pennies, within a more extended pile of pennies].

What determines whether a given DNA site is nuclease hypersensitive? Might this be part of a larger coherent dynamic structure centered in this region?

One of us (HMS) has proposed intercalation to occur within the centers of premeltons – these being emergent coherent dynamic structures that form with different probabilities and have different lifetimes in particular regions of long chain DNA. Premeltons may be related to discrete breathers, mathematical entities well known to the nonlinear scientist.

We will discuss the structure and dynamics of premeltons, their role in nucleating DNA structural phase transitions, and the broader implications premeltons have in molecular biology in subsequent communications.

Henry Sobell
sobell@localnet.com

Alwyn Scott
rover@theriver.com