Determining structural and kinetic pathways for non-canonical DNA structures with time-resolved X-ray solution scattering

DOI

We propose an ESRF beamtime to study pH-driven DNA structural transitions using time-resolved X-ray solution scattering (TRXSS). Our focus is on the structural pathways from Watson-Crick (WC) double-stranded DNA (dsDNA) to non-canonical i-motif and G-quadruplex (G-quad) structures. These non-canonical DNA structures play vital roles in biology such as regulation of gene expression and telomere maintenance. While their thermodynamics are understood, their kinetics, especially in competition with WC dsDNA, are less explored. We plan to use a visible-light-sensitive photoacid to induce pH changes with a nanosecond laser and monitor dsDNA dissociation and i-motif and G-quad formation kinetics with TRXSS. Complementary Molecular Dynamics simulations will use the TRXSS results to examine the structural trajectory along the kinetic pathways. Our study aims to unveil potential intermediates involved in dsDNA dissociation and provide insights into nucleic acid structural transitions.

Identifier
DOI https://doi.org/10.15151/ESRF-ES-1850578548
Metadata Access https://icatplus.esrf.fr/oaipmh/request?verb=GetRecord&metadataPrefix=oai_datacite&identifier=oai:icatplus.esrf.fr:inv/1850578548
Provenance
Creator Madeline HO ORCID logo; Michael MARA ORCID logo; Adam NIJHAWAN; Kevin KOHLSTEDT ORCID logo; Matteo LEVANTINO ORCID logo
Publisher ESRF (European Synchrotron Radiation Facility)
Publication Year 2027
Rights CC-BY-4.0; https://creativecommons.org/licenses/by/4.0
OpenAccess true
Representation
Resource Type Data from large facility measurement; Collection
Discipline Particles, Nuclei and Fields