Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Baylor researchers unravel mystery of DNA conformation

15.07.2009
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 DNA, but the model pictured is a stiff snapshot of idealized DNA.

As researchers from Baylor College of Medicine (www.bcm.edu) and the University of Houston (www.uh.edu) 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 DNA replication, 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 (http://www.bcm.edu/molvir/faculty/elz.htm), associate professor of molecular virology 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 (http://www.chem.uh.edu/Faculty/Pettitt/Research/) 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."

Support for this work came from the Robert A. Welch Foundation, the National Institutes of Health and the Keck Center for Interdisciplinary Bioscience Training of the Gulf Coast Consortia. The computations were performed in part using the Teragrid and the Molecular Science Computing 85 Facility in the William R. Wiley Environmental Molecular Sciences Laboratory, sponsored by the U.S. Department of Energy's Office of Biological and Environmental Research and located at the Pacific Northwest National Laboratory.

Glenna Picton | EurekAlert!
Further information:
http://www.bcm.edu/news
http://www.bcm.edu/fromthelab

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>