Understanding the Properties of Supercoiled DNA

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here researchers from Baylor College of Medicine use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA MiniVector topoisomers with defined degrees of supercoiling. Their results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, they uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, the researchers also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. This integrated approach reveals the three-dimensional structures of DNA that are essential for its function.

Reference

Irobalieva RN, Fogg JM, Catanese DJ, Sutthibutpong T, Chen M, Barker AK, Ludtke SJ, Harris SA, Schmid MF, Chiu W, Zechiedrich L. (2015) Structural Diversity of supercoiled DNA. Nature Comm [Epub ahead of print]. [article]