Chiral effects in DNA supercoiling
Seminar Room 1, Newton Institute
Supercoiling is a topological property of DNA which is known to be crucially important in the genetic regulation of virtually every living cell. Electrostatic interactions play a fundamental role in determining the conformation of DNA molecules. They are generally taken into account assuming that the charge is homogeneously smeared on the surface of DNA molecules. We developed a theory that instead takes into account the helical pattern of charge on the DNA molecular surfaces. We find that the intrinsic chirality of the charge structures gives rise to important and non trivial phenomena. Crucially, it determines an asymmetry in the energetics of DNA-DNA crossovers: right-handed crossings, occurring in positively supercoiled molecules are more stable than left-handed ones, which occur in negatively supercoiled molecules. We explored the consequences of this fact first by developing a theory of spontaneous DNA braid formation, and then applying it to closed loop DNA supercoilin g and single-molecule DNA micromanipulation experiments. The theory can give an account of some yet unexplained observations and biological facts. It gives a plausible explanation for the occurrence of tight supercoiling of DNA loops observed in cryo-EM and AFM images in high ionic strength environment. It can shed light on the preference for positive supercoiling in hyperthermophylic bacteria and archea. Finally, it induces to reinterpret classical experiments that show that divalent metal ions overwind DNA. The biological implications of these important facts could be very important, and are yet to be fully explored.