How does DNA operate to drive cell activities?

A research group from Baylor College of Medicine revealed in unparalleled detail the three-dimensional structure of biologically active DNA. Their report is published in the journal Nature Communications online.
"The beautiful double-helical structure we all know and love is not the actual active form of DNA," said Dr. Lynn Zechiedrich, professor in the department of molecular virology and microbiology, and co-contributing author with Dr. Wah Chiu, professor in the Verna and Marrs McLean Department of Biochemistry and Molecular Biology.
Chiu and Zechiedrich, cooperating with Dr. Steven Ludtke and Dr. Michael Schmid, who is also at Baylor College of Medicine, and Dr. Sarah A. Harris of the University of Leeds in the United Kingdom, examined tiny DNA minicircles containing only 336 base pairs, using methods from chemistry, physics, math and computer modeling. Base pairs are the building blocks of genetic material.
Previous studies were on short fragments of linear DNA, but human DNA is constantly moving around in our body, and it coils and uncoils. Researchers can't coil linear DNA and study it, so they had to make circles so the ends would trap the different degrees of winding, according to Zechiedrich.
In the human body, each cell holds about a meter of DNA which is ten million times longer than the tiny circles the team made. In the research, the researchers wound or unwound a single turn when the DNA double helix comprising their circles and used very powerful microscopes to see how the winding changed what the circles looked like.
They did a test to ensure the tiny twisted up DNA circles that they made in the lab were biologically active. They used purified human topoisomerase II alpha. It's an essential enzyme that manipulates DNA and important target of anticancer drugs. The results indicate that the circles must look and act like the much longer DNA that topoisomerases encounter in human cells.
"Being able to observe individual DNA circles allows us to understand the different structures of biologically active DNA. Each of these different structures facilitates how DNA interacts with proteins, other DNA and RNA, and anticancer drugs, adapting to the cell processes required," said Dr. Jonathan Fogg, the other lead author of the publication, also of Baylor College of Medicine.
The researchers hoped to see the opening of base pairs when the DNA was underwound, but they were surprised to see the opening for the overwound DNA. They supposed this disruption of base pairs may cause flexible hinges, allowing the DNA to sharply bend, and it may help to explain how a meter of DNA can be pushed into a single human cell.
What the researchers will be aimed at is to add other components of the cell or anticancer drugs to figure out how the DNA shapes change. More researchers are joining in to get new findings.
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