Seunghee Cho

Bio: Seunghee Cho is an academic researcher from Sungkyunkwan University. The author has an hindex of 1, co-authored 1 publications receiving 3 citations.

Computational Approaches to Predict the Non-canonical DNAs

Abstract: Although most nucleotides in the genome form canonical double-stranded B-DNA, many repeated sequences transiently present as non-canonical conformations (non-B DNA) such as triplexes, quadruplexes, Z-DNA, cruciforms, and slipped/hairpins. Those noncanonical DNAs (ncDNAs) are not only associated with many genetic events such as replication, transcription, and recombination, but are also related to the genetic instability that results in the predisposition to disease. Due to the crucial roles of ncDNAs in cellular and genetic functions, various computational methods have been implemented to predict sequence motifs that generate ncDNA. Here, we review strategies for the identification of ncDNA motifs across the whole genome, which is necessary for further understanding and investigation of the structure and function of ncDNAs. There is a great demand for computational prediction of non-canonical DNAs that play key functional roles in gene expression and genome biology. In this study, we review the currently available computational methods for predicting the non-canonical DNAs in the genome. Current studies not only provide an insight into the computational methods for predicting the secondary structures of DNA but also increase our understanding of the roles of non-canonical DNA in the genome.

Unraveling the Regulatory G-Quadruplex Puzzle: Lessons From Genome and Transcriptome-Wide Studies.

Abstract: G-quadruplexes (G4s) are among the best-characterized DNA secondary structures and are enriched in regulatory regions, especially promoters, of several prokaryote and eukaryote genomes, indicating a possible role in cis regulation of genes. Many studies have focused on evaluating the impact of specific G4-forming sequences in the promoter regions of genes. However, the lack of correlation between the presence of G4s and the functional impact on cis gene regulation, evidenced by the variable expression fold change in the presence of G4 stabilizers, shows that not all G4s affect transcription in the same manner. This indicates that the regulatory effect of the G4 is significantly influenced by its position, the surrounding DNA topology, and other environmental factors within the cell. In this review, we compare individual gene studies with high-throughput differential expression studies to highlight the importance of formulating a combined approach that can be applied in humans, bacteria, and viruses to better understand the effect of G4-mediated gene regulation.

Molecular Packing Interaction in DNA Crystals

Abstract: DNA crystallography provides essential structural information to understand the biochemical and biological functions of oligonucleotides. Therefore, it is necessary to understand the factors affecting crystallization of DNA to develop a strategy for production of diffraction-quality DNA crystals. We analyzed key factors affecting intermolecular interactions in 509 DNA crystals from the Nucleic Acid Database and Protein Databank. Packing interactions in DNA crystals were classified into four categories based on the intermolecular hydrogen bonds in base or backbone, and their correlations with other factors were analyzed. From this analysis, we confirmed that hydrogen bonding between terminal end and mid-region is most common in crystal packing and in high-resolution crystal structures. Interestingly, P212121 is highly preferred in DNA crystals in general, but the P61 space group is relatively abundant in A-DNA crystals. Accordingly, P212121 contains more terminal end-mid-region interactions than other space groups, confirming the significance of this interaction. While metals play a role in the production of a good crystal in B-DNA conformation, their effect is not significant in other conformations. From these analyses, we found that packing interaction and other factors have a strong influence on the quality of DNA crystals and provide key information to predict crystal growth of candidate oligonucleotides.

An updated overview of experimental and computational approaches to identify non-canonical DNA/RNA structures with emphasis on G-quadruplexes and R-loops

Abstract: Abstract Multiple types of non-canonical nucleic acid structures play essential roles in DNA recombination and replication, transcription, and genomic instability and have been associated with several human diseases. Thus, an increasing number of experimental and bioinformatics methods have been developed to identify these structures. To date, most reviews have focused on the features of non-canonical DNA/RNA structure formation, experimental approaches to mapping these structures, and the association of these structures with diseases. In addition, two reviews of computational algorithms for the prediction of non-canonical nucleic acid structures have been published. One of these reviews focused only on computational approaches for G4 detection until 2020. The other mainly summarized the computational tools for predicting cruciform, H-DNA and Z-DNA, in which the algorithms discussed were published before 2012. Since then, several experimental and computational methods have been developed. However, a systematic review including the conformation, sequencing mapping methods and computational prediction strategies for these structures has not yet been published. The purpose of this review is to provide an updated overview of conformation, current sequencing technologies and computational identification methods for non-canonical nucleic acid structures, as well as their strengths and weaknesses. We expect that this review will aid in understanding how these structures are characterised and how they contribute to related biological processes and diseases.

MD-TSPC4: Computational Method for Predicting the Thermal Stability of I-Motif.

Abstract: I-Motif is a tetrameric cytosine-rich DNA structure with hemi-protonated cytosine: cytosine base pairs. Recent evidence showed that i-motif structures in human cells play regulatory roles in the genome. Therefore, characterization of novel i-motifs and investigation of their functional implication are urgently needed for comprehensive understanding of their roles in gene regulation. However, considering the complications of experimental investigation of i-motifs and the large number of putative i-motifs in the genome, development of an in silico tool for the characterization of i-motifs in the high throughput scale is necessary. We developed a novel computation method, MD-TSPC4, to predict the thermal stability of i-motifs based on molecular modeling and molecular dynamic simulation. By assuming that the flexibility of loops in i-motifs correlated with thermal stability within certain temperature ranges, we evaluated the correlation between the root mean square deviations (RMSDs) of model structures and the thermal stability as the experimentally obtained melting temperature (Tm). Based on this correlation, we propose an equation for Tm prediction from RMSD. We expect this method can be useful for estimating the overall structure and stability of putative i-motifs in the genome, which can be a starting point of further structural and functional studies of i-motifs.