Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia
*Corresponding author: Pozmogova G, Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia, Email: firstname.lastname@example.org
Submission: March 14, 2018;Published: April 04, 2018
Volume1 Issue3 April 2018
Abberant hypomethylation in DNA regions with noncanonical folding potential (ncDNA motifs) is believed to predetermine tumor development - presumably, by facilitating G-quadruplex (G4) and/or i-motif (IM) formation via altering nucleosome positioning (stable G4s induce subsequent genomic rearrangements). We questioned whether CpG methylation per se affects the dsDNA-ncDNA equilibrium. Thermodynamic studies of genomic and model oligonucleotides with methylated CpG sites at different positions are reported. The genomic oligonucleotides analyzed in this work are DNA fragments with reportedly different methylation statuses in colorectal cancer and normal cells. Free energies of duplex, ncDNA formation from single strands were calculated based on melting curve analyses. Polyethylenglycole was used to imitate crowding effect. Our results suggest that CpG methylation may alter the energetic barrier for dsDNA-IM transitions.
Keywords: DNA secondary structures; Methylation; G-quadruplexes; i-motifs; Thermodynamic stability; Molecular crowding
Abbreviations: CD: Circular Dichroism; CGI: Cpg Islands; Etbr: Ethidium Bromide; G4: G-Quadruplex; HPLC: High Performance Liquid Chromatography; IM: Intercalated Motif (I-Motif); MALDI-TOF; MS: Matrix Assisted Laser Desorption Ionization: Time of Flight Mass Spectrometry; Ncdna: Noncanonical DNA Structures; ON: Oligonucleotide; PEG: Polyethylene Glycol; RRT: Rotational Relaxation Time; TDS: Thermal Difference Spectrum