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Nanotech tools yield DNA transcription breakthrough

Rutgers researcher Richard H. Ebright and his collaborators have resolved key questions regarding transcription, the fundamental life process that was the subject of the 2006 Nobel Prize in Chemistry.

Transcription is the first step in the process cells employ to read and carry out the out instructions contained in genes. Transcription is carried out by a molecular machine known as RNA polymerase, which synthesizes an RNA copy of the information in DNA.

Two papers by Ebright and collaborators in the Nov. 17 issue of the journal Science define for the first time the mechanisms by which the machine begins synthesis of RNA and then breaks free from its initial binding site to move along DNA to continue synthesizing RNA.

The results establish that during transcription initiation the machine remains stationary at its initial binding site and "reels in" adjacent DNA segments, unwinding these segments and pulling the unwound DNA strands into itself. This remarkable mechanism, termed "DNA scrunching," enables the machine to acquire and accumulate the energy it needs to break its binding interactions with the initial binding site, and to begin to move down the gene.

"Our findings were made possible by newly developed, single-molecule methods," said Ebright, a Howard Hughes Medical Institute investigator and professor of chemistry and chemical biology at Rutgers, The State University of New Jersey. "These methods enabled us to analyze and manipulate individual molecules of the machine, one-by-one, as they carried out reactions."

The discoveries significantly advance our understanding of the structure and function of the molecular machine that carries out transcription, setting the stage for new opportunities in combating the bacterial diseases that kill 13 million persons each year worldwide.

"For six decades, antibiotics have been our bulwark against bacterial infectious diseases, but this bulwark now is collapsin
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Source:Rutgers, the State University of New Jersey


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