Presented as a Conference Poster at the conference on " DNA, The Double Helix, FortyYears: Perspective and Prospecitive.", Green College - University of Oxford, University of Illinois - College of Medicine, and the New York Academy of Sciences, Chicago, Illinois, October 15, 1993. 

"OPENING THE DOUBLE HELIX TO ACTIVATE DNA."

John H. Frenster
Dept. Medicine
Stanford University
Atherton, CA 94027-5446 

Abstract:
The double helix configuration of DNA is well-established within isolated DNA molecules, but within in-situ DNA molecules (Frenster JH: Ann. N.Y. Acad. Sci. 567: 334-336 (August 4, 1989) DNA displays transcription bubbles and replication forks that are clear departures from the double helix state. These DNA openings correlate with DNA activity (Frenster JH: Cancer Research 31: 1128-1133 (August, 1971), and the conditions affecting their gene location and timing within the cell cycle have been studied within human bone marrow cells after probe insertion and DNase-I digestion (Nakatsu SL, Masek MA, Landrum S, Frenster JH: Nature 248: 334-335 (March 22, 1974). Probe sites range from 25 to 700 nm. in length, and correlate most highly with uridine-H3 and thymidine-H3 incorporation sites. Both RNA and protein molecules may play roles in initiating such helix openings (1-5).

Conclusions:
Although isolated DNA molecules are found in the double-helical configuration, DNA molecules within cells display openings of the double helix as transcription bubbles during RNA synthesis and replication forks during DNA synthesis. Epigenetic controls of genetic activity are mediated by RNA and protein molecules which bind preferentially to single-stranded DNA within discrete gene loci, thereby activating such DNA as a template for RNA synthesis and gene expression.

Additional References:
1. Frenster JH, Ultrastuctural Continuity between Active and Repressed Chromatin, Nature 205: 1341-1342 (1965).

2. Frenster JH, Nuclear Polyanions as De-Repressors of Synthesis of RNA, Nature 206: 680-683 (1965).

3. Frenster JH, A Model of Specific De-Repression within Interphase Chromatin, Nature 206: 1269-1270 (1965).

4. Frenster JH, Localized Strand Separations within DNA during Selective Transcription, Nature 208: 894-896 (1965).

5. Frenster JH, Correlation of the Binding to DNA Loops or to DNA Helices with the Effect on RNA Synthesis, Nature 208: 1093-1094 (1965).

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