Tuesday, November 21, 2006
UCLA researchers in collaboration with researchers at Rutgers University have solved longstanding mysteries surrounding DNA transcription, the first step in carrying out instructions contained in our genes. The breakthrough described in an article in the November 17 issue of the journal Science reveals important structural information about the gyrations of DNA during transcription and the effects of those gyrations on the process.
The discoveries, which inform our understanding of the structure and mechanics of RNAP - an enzyme responsible for making RNA from a DNA or RNA template - can help set the stage for new opportunities in combating bacterial diseases that kill 13 million people worldwide each year.
The researchers used single-molecule spectroscopy to monitor the transfer of energy between - and hence the distance separating - pairs of fluorescent chemical tags attached to key structural elements of RNAP and the DNA double helix during initiation of the transcription process.
Continued at "Researchers Unravel A Mystery About DNA"
Based on "Initial Transcription by RNA Polymerase Proceeds Through a DNA-Scrunching Mechanism" by Richard H. Ebright (homepage) et al.
Using fluorescence resonance energy transfer to monitor distances within single molecules of abortively initiating transcription initiation complexes, we show that initial transcription proceeds through a "scrunching" mechanism, in which RNA polymerase (RNAP) remains fixed on promoter DNA and pulls downstream DNA into itself and past its active center. We show further that putative alternative mechanisms for RNAP active-center translocation in initial transcription, involving "transient excursions" of RNAP relative to DNA or "inchworming" of RNAP relative to DNA, do not occur. The results support a model in which a stressed intermediate, with DNA-unwinding stress and DNA-compaction stress, is formed during initial transcription, and in which accumulated stress is used to drive breakage of interactions between RNAP and promoter DNA and between RNAP and initiation factors during promoter escape.
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