Unraveling the Biophysics of Non-Canonical Nucleic Acid Structures: Implications for Cellular Function and Disease

Non-canonical nucleic acid structures, diverging from the classical double helix, have garnered significant attention for their unique roles in cellular biology. These structures include G-quadruplexes, cruciform DNA, R-loops, i-Motifs, and triplex DNA, characterized by distinct folding patterns and complex biophysical interactions. Increasingly recognized for their regulatory functions, these structures play pivotal roles in gene expression, replication, genome stability, and repeat-expansion diseases. For instance, G-quadruplexes and triplex DNA, involving Hoogsteen base pairing, expand the structural diversity of nucleic acids, underscoring their biological significance.

Emphasizing the biophysics themes, this Research Topic will elucidate the mechanistic pathways and energetic landscapes governing the formation, stabilization, and function of non-canonical nucleic acids. Advanced biophysical techniques offer invaluable insights into these structures' conformational dynamics and interactions, linking them to critical cellular processes and pathological conditions, such as cancer, neurodegenerative diseases, and genetic disorders. Understanding these aspects is crucial for developing novel therapeutic strategies targeting non-canonical structures, providing new avenues for disease treatment and prevention.

This collection will accept Original Research, Reviews, and Perspectives that explore the formation, stability, and biological roles of non-canonical nucleic acid structures. We particularly welcome studies employing cutting-edge biophysical methods and interdisciplinary approaches. Manuscripts should provide comprehensive data, robust analysis, and clear implications for future research and clinical applications, fostering interdisciplinary dialogue and advancing our understanding of non-canonical nucleic acids in the context of innovative diagnostics and therapeutic strategies.

Themes of interest include but are not limited to the following:

• Biophysical characterization of non-canonical nucleic acid structures

• Conformational dynamics and stability of G-quadruplexes, i-Motifs, cruciform DNA, R-loops, and triplex DNA

• Role of non-canonical nucleic acids in gene expression regulation and genome stability

• High-resolution imaging and single-molecule techniques in studying nucleic acids

• Bioinformatics approaches for genome-wide mapping of non-canonical structures

• Mechanisms of non-canonical structure formation and dissolution

• Impact of non-canonical nucleic acids on disease pathogenesis, including cancer and neurodegenerative disorders

• Development of novel biomarkers and therapeutic targets based on non-canonical structures

• Interdisciplinary approaches combining biophysics, molecular biology, and computational modeling

Keywords: Non-canonical Nucleic acids, G-quadruplexes, Expandable repeats, Gene expression, R-loops

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.