Patience, My Dear Polymerase

When RNA polymerase II (Pol II) transcribes DNA to messenger RNA in eukaryotes, it must overcome the physical barrier imposed by the wrapping of DNA around histones. It has remained a mystery whether the enzyme actively unwraps the DNA to gain access or whether Pol II waits for the DNA-histone complex to locally unwrap itself before making a move. Now, a group led by Carlos Bustamante of the University of California, Berkeley, has used optical tweezers to follow a single Pol II molecule as it processes DNA wrapped around histones and anchored between two trapped beads (Science 2009, 325, 626). As Pol II moves along DNA, it pauses at the DNA-histone complex. Bustamante and colleagues found that the frequency and length of the Pol II pauses are consistent with Pol II waiting for DNA to unwrap. "The polymerase, rather than actively separating DNA from histones, functions instead as a ratchet" that seizes on unwrapped DNA and transcribes it before it becomes inaccessible again, then waits for the next opportunity, the authors write. Modulation of DNA wrapping and unwrapping around histones could be critical for transcription regulation, they conclude.