Non-Canonical Nucleic Acid Structures

    Certain DNA sequences have the capacity to adopt alternative structures to the
canonical Watson-Crick double-helical “B-form” of DNA, and RNA sequences are also
know to form a wide range of structures apart from the well established A-form double
helix. These non-canonical nucleic acid structures are proposed to play important roles
in a wide range of cellular functions, and have also been incorporated into the design of
sensors and nanomaterials.


Our current work focuses on three classes of these non-canonical nucleic acid
structures:


Four-stranded G-quadruplex DNA (G4-DNA) structures, which can form in G-rich
sequences, particularly in the presence of certain cations such as Na+ and K+ .
Three-stranded G-Triplex DNA structures, which may form from “truncated” G4-
DNA-forming sequences, and which have not been well studied to date.
Triple-stranded H-DNA structures, which can form from mirror repeat
poly(purine)/poly(pyrimidine) sequences.


Our work focuses on answering some fundamental questions about these non-canonical
structures:


• What sequences and what environmental conditions favor the formation of these
non-canonical structures?
• What are the dynamics of formation and resolution of these structures in vitro and
in vivo, and can small molecules affect these processes?
• What effect does the formation of these structures have on the biological processes
of DNA replication, transcription, and translation, and can covalent or non-covalent
associations with these structures by small molecules provide a means to selectively
target these processes?

 


For additional information, see the following representative publications:


• McBrayer, D.; Schoonover, M.; Long, K.; Escobedo, R.; Kerwin, S. M. “ N-
methylmesoporphyrin IX Exhibits G-Quadruplex-Specific Photocleavage Activity”
ChemBioChem 2019, 20, 1924-1927.
• del Mundo, I. M. A.; Zewail-Foote, M.; Kerwin, S. M.; Vasquez, K. M. Alternative DNA
structure formation in the mutagenic human c-MYC promoter. Nucl. Acids Res. 2017;
45(8):4929-43
• Schoonover, M.; Kerwin, S. M.“G-Quadruplex DNA Cleavage Preference and
Identification of a Perylene Diimide G-Quadruplex Photocleavage Agent Using a Rapid
Fluorescent Assay” Bioorg. Med. Chem. 2012, 20, 6904–6918.