Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Expanding the Structural Diversity of DNA Beyond the Double Helix

The iconic model of DNA is the Watson-Crick double helix, but it can form other types of structures. The extent of the structural diversity of DNA is not well understood. We are interested in discovering new types of DNA structure through the screening of a library of short DNA sequences and subsequent structure determination for those that crystallize. From the screen, we aim to create a library of 3D DNA crystal structures and identify previously unknown DNA motifs. We report 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. This is the first fold-back structure that forms a tetramer and is specific for divalent cations. 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 (Chu et al., 2018). Fold-back structures are biologically relevant since they have been observed in promoter regions of development genes (Mir et al., 2017). d(CCAGGCTGCAA) features a Ba2+-stabilized G-quadruplex, which is flanked on either side by a base triple formed through noncanonical interactions and an i-motif. This tetramer 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 two structures demonstrate that DNA assemblies beyond the traditional double helix exist and suggest that DNA can form even more diverse structures.

This research has been supported by the NSF Career Award 1149665.

bety-chu-fig.gif References

    Chu, B., Zhang, D., Hwang, W., and Paukstelis, P. J. (2018) Crystal structure of a tetrameric DNA fold-back quadruplex, J. Am. Chem. Soc. 140, 16291-16298.

    Mir, B., Serrano, I., Buitrago, D., Orozco, M., Escaja, N., and Gonzalez, C. (2017) Prevalent sequences in the human genome can form mini i-motif structures at physiological pH., J. Am. Chem. Soc. 139, 13985-13988.

Betty Chu
Paul J. Paukstelis

University of Maryland
Department of Chemistry and Biochemistry
Center for Biomolecular Structure and Organization
College Park, MD 20742

Ph: (301) 405-9933
Email: paukstel@umd.edu