Abstract
DNA folding is a core phenomenon in genome packaging within a nucleus. Such a phenomenon is induced by polyelectrolyte complexation between anionic DNA and cationic proteins of histones. In this regard, complexes formed between DNA and cationic polyelectrolytes have been investigated as models to gain insight into genome packaging. Upon complexation, DNA undergoes folding to reduce its occupied volume, which often results in multi-complex associated aggregates. However, when cationic copolymers comprising a polycation block and a neutral hydrophilic polymer block are used instead, DNA undergoes folding as a single molecule within a spontaneously formed polyplex micelle (PM), thereby allowing the observation of the higher-order structures that DNA forms. The DNA complex forms polymorphic structures, including globular, rod-shaped, and ring-shaped (toroidal) structures. This review focuses on the polymorphism of DNA, particularly, to elucidate when, how, and why DNA organizes into these structures with cationic copolymers. The interactions between DNA and the copolymers, and the specific nature of DNA in rigidity; i.e., rigid but foldable, play significant roles in the observed polymorphism. Moreover, PMs serve as potential gene vectors for systemic application. The significance of the controlled DNA folding for such an application is addressed briefly in the last part.
Highlights
Human DNA, which is almost 2 m long, is packaged in a cellular nucleus and forms chromosomes approximately 10 μm in size through the integration of hierarchical higher-order structures
The peptides with their positive charges evenly distributed along the chain, KSKSKSKSKS, bound to DNA stronger and resulted in disordered using PEG12k-b-poly{N’-[N-(2- aminoethyl)-2-aminoethyl]aspartamide}61 (PEG-b-P(Asp(DET)) found that the rod-shaped structure was selectively formed when plasmid DNA (pDNA) and the block copolymers were mixed in the absence of salt (Figure 5b)
It was revealed that individual DNA inherently forms higher-order structures, such as rod-folding and ring-spooling, and otherwise results in the collapsing into globular that occurs when the condensation process instantaneously proceeds
Summary
Human DNA, which is almost 2 m long, is packaged in a cellular nucleus and forms chromosomes approximately 10 μm in size through the integration of hierarchical higher-order structures. This is an essential question in the study of life sciences To tackle this question, the nucleosome, a complex formed between individual DNA and a group of histones, can be highlighted, as it is the key basis for the organization of the hierarchical higher-order structures. Polyion complexation with single-stranded DNA tends to result in micrometer-sized droplets in contrast to the double-stranded version that often results in precipitation [10,11,12]. Among these DNA forms, this review mainly deals with giant double-stranded DNA with a length of several thousand base pairs and focuses on its conformational changes upon polyion complexation. Significances of controlled DNA folding structures in the development of gene vectors and some critical issues residing there are addressed briefly
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