Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 10, Pages 3645-3650Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409059102
Keywords
activation; gene regulation; repression
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Funding
- NIGMS NIH HHS [R01 GM 058617, R01 GM 054692, R01 GM058617, R01 GM054692] Funding Source: Medline
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Gene-regulatory complexes often require that pairs of DNA-bound proteins interact by looping-out short (often approximate to 100-bp) stretches of DNA. The loops can vary in detailed length and sequence and, thus, in total helical twist, which radically alters their geometry. How this variability is accommodated structurally is not known. Here we show that the inherent twistability of 89- to 105-bp DNA circles exceeds theoretical expectation by up to 400-fold. These results can be explained only by greatly enhanced DNA flexibility, not by permanent bends. They invalidate the use of classic theories of flexibility for understanding sharp DNA looping but support predictions of two recent theories. Our findings imply an active role for DNA flexibility in loop formation and suggest that variability in the detailed helical twist of regulatory loops is accommodated naturally by the inherent twistability of the DNA.
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