Molecular models of DNA

About: Molecular models of DNA is a research topic. Over the lifetime, 300 publications have been published within this topic receiving 16805 citations.

Tuning DNA compaction

Abstract: DNA compaction is the collapse of long DNA chains into well-organized condensates of complex, hierarchical nanostructure induced by the presence of cationic agents. Although much progress has been made in understanding underlying interaction mechanisms of in vivo DNA compaction, the interplay of the myriad compaction agents and their types of interactions with DNA still raise a wealth of unanswered, fundamental questions. In particular, the hierarchical organization of chromatin is widely unclear. There, the DNA is first wrapped around histone cores and the formed beads-on-a-string structure is successively shifted towards higher order forms of chromatin structure. The latter process involves linker histones as major antagonists.Here, new results are presented that are derived from bio-mimetic investigations of the simplest possible DNA compaction model system containing only dendrimers, which can be viewed as uniformly charged cationic nanospheres, and unspecific, polydisperse DNA. Small angle X-ray (micro-)diffraction is employed as a principle method of analysis that accesses relevant molecular length scales. Targeting a quantitative understanding of compaction mechanisms, X-ray (micro-)diffraction measurements performed under laminar flow conditions in hydrodynamic focusing microfluidic devices provides microscale control of the self-assembly process. In addition, the method enables time-resolved access to structure formation in situ, in particular to transient intermediate states.Utilizing the high level of control over dendrimer size and charge, DNA compaction is systematically tuned and analyzed in detail. Results show that dendrimers bridge the entire spectrum of biological condensation agents from small cations, such as spermine/spermidine encountered in viruses, to the much larger histone proteins found in eukaryotic cells. Despite its simplicity, the dendrimer/DNA system reproduces characteristic features of DNA compaction in vivo. In particular, PAMAM 6 dendrimers (having a size and charge comparable to histone core proteins) induce a complete wrapping of the DNA around the cation. As such, PAMAM 6/DNA entities are structurally artificial equivalents of nucleosome core particles. For cationic dendrimers having an intermediate size and charge, which is conveniently between that of small multivalent organic cations and larger histone-like proteins, an alternate route of DNA compaction aside from the established salt or macroion condensation is observed in microflow below the isoelectric point, where DNA is in excess of dendrimers.In addition, the phenomenon of charge-induced dendrimer swelling has been experimentally quantified in detail over a wide range of generations. Results clearly show highly predictable, charge-induced changes of the dendrimer conformation and therefore eliminate the discrepancy between theory and experiments that previously existed in literature.Besides artificial model-proteins, the interaction of linker histones H1 and DNA has been studied in microflow. The time-resolved access to struture formation dynamics clearly shows that the interaction of H1 with DNA is a two step process: an initial unspecific binding of H1 to DNA is followed by a rearrangement of molecules in the formed complexes. Results suggest that the conformational transition of H1 tails from their rather extended conformation, in aqueous solution, to their fully folded state, upon interaction with DNA, is most likely the motor of the conformational phase transition of H1/DNA assemblies.Results obtained in this thesis are expected to have a direct bearing on the understanding of the hierarchical organization of chromatin in vivo. Underlying concepts and techniques may be generalized and used to experimentally address also other relevant protein/DNA systems. Moreover, the studied systems are of inherent importance to the field of biotechnology and are expected to contribute towards the design of new vectors for DNA gene delivery.

Dna model teaching materia and learning method using the same

Abstract: PROBLEM TO BE SOLVED: To provide a DNA model which enables a user to learn the principle and process of replication of DNA through simulation by demonstration and into which a message including an arbitrary long text can be encrypted and written, and a manufacturing method thereof.SOLUTION: A double helical backbone of DNA or a backbone obtained by expanding and parallelizing it is made of ropes or flexible tubes, and base pairs separable at intermediate positions are arranged on the backbone. A user can learn, through simulation by demonstration, the fundamental principle of DNA replication and the process of DNA replication including discontinuous replication due to Okazaki fragments in lagging chains by utilizing flexibility of the backbone to separate a double chain into two single chains, and a decoding table created by simulating a biological genetic code dictionary is used to encrypt an arbitrary message by a base sequence to write the message into the DNA model.

Topological Differences in the Interaction of Human DNA Topoisomerase I with DNA–Histone Complexes Modified by cis - and trans -DDP

Abstract: We show that the trefoil, figure-eight knot, and mini circular closed DNA are formed by the reaction of cis-DDP-modified φX174DNA–histoneLNCaP complexes as a new nucleosome model with human DNA topoisomease I. The yields from cis-DDP-modified complexes were far higher than that of trans-DDP. The topologically-distinct invariant DNA such as the trefoil and figure-eight knot are not produced in the reaction of DNA topo I with φX174DNA–histoneLNCaP complexes that are not modified by platinum. Therefore, the anti-cancer activity of cis-DDP may be related to the production of the trefoil, figure-eight knot, and mini circular closed DNA forms in the living cell. We subsequently demonstrate that the yield mechanism and identification of the topologically-distinct invariant DNA can be explained by the topological method using a Jones polynomial and recombination through the topo I path intra-twisted looped DNA model. These results suggest that the distinguishing of anti-neoplastic activity of cis- and trans-DDP can be partially explained by the distinct topologies of DNA, trefoil, figure-eight knot, and mini circular closed DNA that they produce.

On DNA modelling : interaction of a double helicoidal structure with viscous bio-fluid

Abstract: The paper aims at extending, utilising and general ising research in nonlinear dynamics of (i) spiral/helicoidal structures, and (ii) viscous. low speed fluid to biomechanical DNA fluid· structure interaction. Employing a nonlinear helicoidal model. the energy stored in a distorted Watson-Crick DNA model subjected to viscous. low speed organic fluid loading is fonnulated. Numerical solutions based on the variational principle are presented for a linearized flow field as examples. Significant dynamical responses such as defonnation components and resultants are discussed. A proposal for matching of DNA sequential characteristics with respect to the nonlinear dynamical responses is outlined in order to reveal infonnation regarding DNA sequencing by means of a fluid-structure dynamical approach.

New Structural Motifs Isohelical to DNA

Abstract: Currently, significant progress has been made in the design and synthesis of site-specific DNA-binding agents that are analogues of the natural pyrrolecarboxamide antibiotics netropsin and distamycin and the bis benzimidazole dye Hoechst 33258 [1–7]. These compounds bind in the minor DNA groove to runs of three to five consecutive AT-base pairs. All of them contain a structural motif in which five-membered aromatic cycles are linked via two sp2-hybridized atoms (Fig. 1). Hereinafter, this structural motif will be referred to as motif I.