EXPLORING THE STRUCTURAL DIVERSITY OF DNA BEYOND THE DOUBLE HELIX
EXPLORING THE STRUCTURAL DIVERSITY OF DNA BEYOND THE DOUBLE HELIX
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Date
2020
Authors
Chu, Betty
Advisor
Paukstelis, Paul J
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Abstract
The iconic model of DNA is the Watson-Crick double helix, but it can form other types of structures. The extent of DNA structural diversity is not well understood. We are interested in discovering new types of DNA structure through the crystal screening and structure determination of a library of oligonucleotide sequences. Through this, we aim to identify previously unobserved motifs that may be biologically relevant and investigate the correlation between the sequence and the structures solved from the library. Furthermore, we can better understand the structural diversity of DNA and sample the different types of motifs formed, as well as the frequency of them. Moreover, from a nanotechnological standpoint, determining new DNA motifs can expand the structure space for rational DNA crystal design to create more precise nanostructures targeted for specific applications. In this dissertation, I will discuss two new crystal structures of single oligonucleotides that interact via noncanonical base pairing. d(CGTAAGGCG) forms a non-G-quadruplex fold-back structure through both Watson-Crick and noncanonical interactions. The tetrameric assembly encloses a central cation binding pocket and features a hexad base pairing arrangement through two C─G─G base triples. We have also determined three variant sequences that form the same structure, suggesting that there is a large number of potential fold-back sequences in genomes. This is of particular biological relevance since fold-back structures have been observed in promoter regions of developmental genes in humans. d(CCAGGCTGCAA) features a barium-stabilized G-quadruplex, which is flanked on either side by a base triple formed through noncanonical interactions and a peripheral i-motif. This structure suggests the necessity of a spacer region to bridge the geometric differences between the G-quadruplex and i-motif. This is the first structure of a hybrid DNA G-quadruplex/i-motif and demonstrates the possibility of the coexistence of G-quadruplexes and i-motifs in a single strand of DNA in genomes. The fold-back quadruplex and hybrid G-quadruplex/i-motif highlight the growing structural diversity of DNA and suggest greater biological roles for non-duplex structures. These structures demonstrate that DNA assemblies beyond the traditional double helix exist and suggest that DNA can form even more diverse structures.