Gene-bender Proteins May Sway To DNA

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Gene-bender Proteins May Sway To DNA

http://www.medicalnewstoday.com/medicalnews.php?newsid=58166

Among the many genes packed into each cell of our body, those that

get turned on, or expressed, are the ones that make us who we are.

Certain proteins do the job of regulating gene expression by

clasping onto key spots of DNA -- the nucleic acid that contains the

genetic instructions.

How does the protein recognize a particular binding site " Structural

changes in both the protein and DNA, sometimes with the DNA within

the complex kinked or sharply bent, allow for the specific contacts

needed for a tight DNA-protein fit.

Scientists think DNA is largely passive in this genetic tango. But

new findings by Anjum Ansari, associate professor of biophysics at

the University of Illinois at Chicago, suggest DNA may not be the

wallflower that many had assumed.

To follow in real time the structural changes that accompany protein-

DNA binding, Ansari and her UIC colleagues used a test protein from

bacteria and applied a laser pulse lasting about 10 billionths of a

second to heat up and disturb the protein-DNA complex. They watched

the dynamics of the bound DNA in response to this perturbation.

Ansari's group was the first to apply the laser temperature-jump

technique to study the dynamics of a protein-DNA complex.

The studies were done in collaboration with Crothers,

Sterling Professor Emeritus of chemistry at Yale University, who

examined the protein-DNA interaction with the more traditional

stopped-flow technique.

" While stopped-flow technique can capture dynamics of biomolecules

occurring on millisecond time-scales or longer, the goal of this

study was to extend the time-resolution down to sub-microseconds. It

gave us a new time window on probing protein-DNA interactions, "

Ansari said.

That broader time window, obtained in combination with the stopped-

flow measurements, provided the first direct observation of DNA

bending when bound to a DNA-bending protein.

" We found that the time-scales on which DNA was bending were very

similar to previously reported time-scales on which individual base-

pairs that hold the two DNA strands together were transiently

breaking. That led us to conclude that the DNA is able to bend or

kink on its own, at weak points created by the transient opening of

base-pairs, and that the protein recognizes and binds tightly to the

bent DNA conformation. "

Conclusions by Ansari and her colleagues deviate slightly from the

conventional dogma that it is the protein that bends the DNA. She

said the results raise important questions about the role that the

DNA " bendability " plays in guiding the correct bending protein to

the appropriate site on the DNA.

Ansari said the research adds to the basic understanding of how

proteins recognize a specific binding site.

" Gaining better insights into protein-DNA interactions that control

all aspects of gene regulation may prove useful for rational design

of drugs to target specific sites on the DNA, whereby one can

ultimately develop better gene-based therapies, " she said.

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The findings appear in the Dec. 5 issue of the Proceedings of the

National Academy of Sciences. Serguei Kuznetsov, research assistant

professor of physics at UIC, is first author on the paper; Ansari

and Crothers are corresponding authors. Other co-authors include

graduate students a Vivas, working with Ansari at UIC, and

Sawako Sugimura, working with Crothers at Yale.