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Biomedical subjects

I M Kulić

Publications and source records attributed to I M Kulić.

4 recordsLinked to original sources

DNA spools under tension.

DNA spools, structures in which DNA is wrapped and helically coiled onto itself or onto a protein core, are ubiquitous in nature. We develop a general theory describing the nonequilibrium behavior of DNA spools under linear tension. Two puzzling and seemingly unrelated recent experimental findings, the sudden quantized unwrapping of nucleosomes and that of DNA toroidal condensates under tension, are theoretically explained and shown to be of the same origin. The study provides new insights into nucleosome and chromatin fiber stability and dynamics.

DNA↗

Chromatin dynamics: nucleosomes go mobile through twist defects.

We study the spontaneous "sliding" of histone spools (nucleosomes) along DNA as a result of thermally activated single base pair twist defects. To this end we map the system onto a suitably extended Frenkel-Kontorova model. Combining results from several recent experiments we are able to estimate the nucleosome mobility without adjustable parameters. Our model shows also how the local mobility is intimately linked to the underlying base pair sequence.

Chromatin↗

Nucleosome repositioning via loop formation.

Active (catalyzed) and passive (intrinsic) nucleosome repositioning is known to be a crucial event during the transcriptional activation of certain eukaryotic genes. Here we consider theoretically the intrinsic mechanism and study in detail the energetics and dynamics of DNA-loop-mediated nucleosome repositioning, as previously proposed by earlier works. The surprising outcome of the present study is the inherent nonlocality of nucleosome motion within this model-being a direct physical consequence of the loop mechanism. On long enough DNA templates the longer jumps dominate over the previously predicted local motion, a fact that contrasts simple diffusive mechanisms considered before. The possible experimental outcome resulting from the considered mechanism is predicted, discussed, and compared to existing experimental findings.

Binding Sites↗

Evaluating polynomials on the molecular level--a novel approach to molecular computers.

In the past few years two fascinating and new scientific fields, the science of DNA-structure and topology and the theory of molecular computers have been growing independently. The main goal of this paper is to establish an interesting connection between them and to propose a novel paradigm for the future construction of DNA-computing devices based on supercoil energetics. The basic principle of the proposed model can also be applied to describe the communication between topologically closed segments in real genomes, which is believed to take part in the complex process of gene regulation. An implementation of the recent model is proposed by which polynomials of one real variable can be evaluated in a simple in vitro recombination assay.

Computers↗