"Opening the Double Helix to Activate DNA."
John H. Frenster,
Dept. Medicine, Stanford University, Atherton, CA 94027-5446
E-mail: frenster@euchromatin.net
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).
Additional References:
0. Electron Microscopy of Human Lymphocytes before and after Activation by PHA (Busch H, 1974).
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