title: Bubble statistics and positioning in superhelically stressed DNA.
abstract: We present a general framework to study the thermodynamic denaturation of double-stranded DNA under superhelical stress. We report calculations of position- and size-dependent opening probabilities for bubbles along the sequence. Our results are obtained from transfer-matrix solutions of the Zimm-Bragg model for unconstrained DNA and of a self-consistent linearization of the Benham model for superhelical DNA. The numerical efficiency of our method allows for the analysis of entire genomes and of random sequences of corresponding length (10(6)-10(9) base pairs). We show that, at physiological conditions, opening in superhelical DNA is strongly cooperative with average bubble sizes of 10(2)-10(3) base pairs (bp), and orders of magnitude higher than in unconstrained DNA. In heterogeneous sequences, the mean degree of base-pair opening is self-averaging, while bubble localization and statistics are dominated by sequence disorder. Compared to random sequences with identical GC-content, genomic DNA has a significantly increased probability to open large bubbles under superhelical stress. These bubbles are frequently located directly upstream of transcription start sites.
authors: Laboratoire de Physique and Centre Blaise Pascal of the École Normale Supérieure de Lyon, Université de Lyon, CNRS UMR 5672, Lyon, France.
authors: Daniel
authors: D
authors: Jost
authors: Asif
authors: A
authors: Zubair
authors: Ralf
authors: R
authors: Everaers
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D009690:Nucleic Acid Conformation; D013314:Stress, Mechanical
chemical_list: D004247:DNA