Sequence Affects the Cyclization of DNA Minicircles

Understanding how the sequence of a DNA molecule affects its dynamic properties is a central problem affecting biochemistry and biotechnology. The process of cyclizing short DNA, as a critical step in molecular cloning, lacks a comprehensive picture of the kinetic process containing sequence information. Researchers at the Sealy Center for Structural Biology and Molecular Biophysics at the University of Texas Medical Branch have elucidated this process by using coarse-grained simulations, enhanced sampling methods, and recent theoretical advances. They are able to identify the types and positions of structural defects during the looping process at a base-pair level. Correlations along a DNA molecule dictate critical sequence positions that can affect the looping rate. Structural defects change the bending elasticity of the DNA molecule from a harmonic to subharmonic potential with respect to bending angles. The researchers explore the subelastic chain as a possible model in loop formation kinetics. A sequence-dependent model is developed to qualitatively predict the relative loop formation time as a function of DNA sequence.

minivectors

(A) Illustration of the cyclization process of a dsDNA with total bp =73. The numbers in the Figure show the bp index. Two overhangs are at nucleotides 63–72 in one strand and nt73–82 in its complementary strand. (B) Free-energy profile of DNA TA as a function of the distance between bp72 and bp82, R72–82. (C) Base pair opening probability of bp11, 25, and 72. ε = 25 kJ/mol. σ = 8.52 Å.

minivectors

(A) Markov model to represent the looping process. (B) Prediction on the looping time for different DNA sequences. T0 is a time unit to match the CG time to real time. The error is <0.01 T0..

Reference

Wang Q, Pettitt BM. (2016) Sequence Affects the Cyclization of DNA Minicircles. J Phys Chem Lett 7(6):1042-6. [abstract]