Book of Abstracts: Albany 2005

category image Volume 22
No. 6
June 2005

Compressed Backbone Hypothesis of B-DNA Fine Structure and Dynamics

The hypothesis of intrinsic backbone compression in B-DNA (CBH), that first emerged from free MD simulations of A-tract induced static bends, assumes that, under physiological conditions, the equilibrium specific length of the sugar-phosphate backbone, considered as a restrained polymer attached to a cylindrical surface, is slightly longer than necessary for optimal base stacking. Such a mismatch would cause a geometric frustration and result in a much more complex behavior of the double helix than it is usually assumed. CBH explains the origin of non-local sequence effects and offers new interpretations to some long-standing puzzles of intrinsically bent DNA. It also changes significantly the common view of DNA dynamics because, under certain conditions, the aforementioned geometric frustration may result in very slow relaxation processes. One of the non-trivial predictions of CBH consisted in the curvature relaxation effect in DNA due to single stranded breaks (nicks). Because of the stipulated backbone compression, the static curvature in A-tract repeats nicked at different positions should be relaxed in a position dependent manner. This prediction has been recently checked experimentally. In contrast to earlier known nick effects, and in agreement with CBH, the gel mobility of curved DNA fragments is increased by single stranded breaks depending regularly upon their position with respect to the expected bend direction. This effect was not anticipated by prevailing theories of DNA structure and it has not been encountered before. It was also partially reproduced in free MD simulations. Analysis of computed curved DNA conformations reveals modulations of local backbone length as measured by distances between some sugar atoms, suggesting that the maximal backbone compression is observed at the inner circumference of the bent DNA.

References and Footnotes
  1. A. K. Mazur J. Am. Chem. Soc. 122, 12778 (2000).
  2. A. K. Mazur J. Biomol. Struct. Dyn. 18, 832 (2001).
  3. A. K. Mazur and D. E. Kamashev Phys. Rev. E 66, 011917 (2002).
  4. D. E. Kamashev and A. K. Mazur Biochemistry 437, 8160 (2004).

Dimitri E. Kamashev
Alexey K. Mazur*

Laboratoire de Biochimie Theorique, CNRS UPR9080
Institut de Biologie Physico-Chimique
13, rue Pierre et Marie Curie
Paris, 75005, France

*Phone: +33[0]
Email: alexey@ibpc.fr