Researchers unravel mystery of DNA conformation

Jul 13, 2009

An iconic photograph (http://img.timeinc.net/time/80days/images/530228.jpg) of Nobel laureates Drs. Francis Crick and James Watson show the pair discussing with a rigid model of the famous double helix.

The interaction represented produced the famous explanation of the structure of , but the model pictured is a stiff snapshot of idealized DNA. As researchers from Baylor College of Medicine and the University of Houston note in a report that appears online in the journal Nucleic Acids Research, DNA is not a stiff or static. It is dynamic with high energy. It exists naturally in a slightly underwound state and its status changes in waves generated by normal cell functions such as , transcription, repair and recombination. DNA is also accompanied by a cloud of counterions (charged particles that neutralize the genetic material's very negative charge) and, of course, the protein macromolecules that affect DNA activity.

"Many models and experiments have been interpreted with the static model," said Dr. Lynn Zechiedrich, associate professor of and microbiology at BCM and a senior author of the report. "But this model does not allow for the fact that DNA in real life is transiently underwound and overwound in its natural state."

DNA appears a perfect spring that can be stretched and then spring back to its original conformation. How far can you stretch it before something happens to the structure and it cannot bounce back? What happens when it is exposed to normal cellular stresses involved in doing its job? That was the problem that Zechiedrich and her colleagues tackled.

Their results also addresses a question posed by another Nobel laureate, the late Dr. Linus Pauling, who asked how the information encoded by the bases could be read if it is sequestered inside the DNA molecular with phosphate molecules on the outside.

It's easy to explain when the cell divides because the double-stranded DNA also divides at the behest of a special enzyme, making its genetic code readily readable.

"Many cellular activities, however, do not involve the separation of the two strands of DNA," said Zechiedrich.

To unravel the problem, former graduate student, Dr. Graham L. Randall, mentored jointly by Zechiedrich and Dr. B. Montgomery Pettitt of UH, simulated 19 independent DNA systems with fixed degrees of underwinding or overwinding, using a special computer analysis started by Petttitt.

They found that when DNA is underwound in the same manner that you might underwind a spring, the forces induce one of two bases - adenine or thymine - to "flip out" of the sequence, thus relieving the stress that the molecule experiences.

"It always happens in the underwound state," said Zechiedrich. "We wanted to know if torsional stress was the force that accounted for the base flipping that others have seen occur, but for which we had no idea where the energy was supplied to do this very big job."

When the base flips out, it relieves the stress on the DNA, which then relaxes the rest of the DNA not involved in the base flipping back to its "perfect spring" state.

When the molecule is overwound, it assumes a "Pauling-like DNA" state in which the DNA turns itself inside out to expose the bases -- much in the way Pauling had predicted.

Zechiedrich and her colleagues theorize that the base flipping, denaturation, and Pauling-like DNA caused by under- and overwinding allows DNA to interact with proteins during processes such as replication, transcription and recombination and allows the code to be read. And back to the idea of the "perfect spring" behavior of the DNA helix - "This notion is entirely wrong," said Zechiedrich. "Underwinding is not equal and opposite to overwinding, as predicted, not by a long shot, that's really a cool result that Graham got."

More information: The report is available free at nar.oxfordjournals.org/cgi/con… 0&resourcetype=HWCIT

Source: Baylor College of Medicine (news : web)

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HenisDov
not rated yet Jul 14, 2009
On the origin of origins, including life:

On The Origin Of Origins

Dark Matter-Energy And %u201CHiggs%u201D?
Energy-Mass Superposition
The Fractal Oneness Of The Universe
All Earth Life Creates and Maintains Genes


A. On Energy, Mass, Gravity, Galaxies Clusters AND Life, A Commonsensible Recapitulation
http://www.the-sc...age#2125
The universe is the archetype of quantum within classical physics, which is the fractal oneness of the universe.

Astronomically there are two physics. A classical physics behaviour of and between galactic clusters, and a quantum physics behaviour WITHIN the galactic clusters.

The onset of big-bang's inflation, the cataclysmic resolution of the Original Superposition, started gravity, with formation - BY DISPERSION - of galactic clusters that behave as classical Newtonian bodies and continuously reconvert their original pre-inflation masses back to energy, thus fueling the galactic clusters expansion, and with endless quantum-within-classical intertwined evolutions WITHIN the clusters in attempt to delay-resist this reconversion.


B. Updated Life's Manifest May 2009
http://www.physfo...ic=14988&st=480&#entry412704
http://www.the-sc...age#2321

All Earth life creates and maintains Genes. Genes, genomes, cellular organisms - All create and maintain genes.

For Nature, Earth's biosphere is one of the many ways of temporarily constraining an amount of ENERGY within a galaxy within a galactic cluster, for thus avoiding, as long as possible, spending this particularly constrained amount as part of the fuel that maintains the clusters expansion.

Genes are THE Earth's organisms and ALL other organisms are their temporary take-offs.

For Nature genes are genes are genes. None are more or less important than the others. Genes and their take-offs, all Earth organisms, are temporary energy packages and the more of them there are the more enhanced is the biosphere, Earth's life, Earth's temporary storage of constrained energy. This is the origin, the archetype, of selected modes of survival.

The early genes came into being by solar energy and lived a very long period solely on solar energy. Metabolic energy, the indirect exploitation of solar energy, evolved at a much later phase in the evolution of Earth's biosphere.

However, essentially it is indeed so. All Earth life, all organisms, create and maintain the genes. Genes, genomes, cellular organisms - all create and maintain genes.


Dov Henis
(Comments from 22nd century)