G-Quadruplex Formation by DNA Sequences Deficient in Guanines: Two Tetrad Parallel Quadruplexes Do Not Fold Intramolecularly

Varování

Publikace nespadá pod Lékařskou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

Autoři	KEJNOVSKA I. STADLBAUER P. TRANTÍREK Lukáš RENCIUK D. GAJARSKÝ Martin KRAFČÍK Daniel PALACKY J. BEDNAROVA K. SPONER J. MERGNY J.L. VORLICKOVA M.
Rok publikování	2021
Druh	Článek v odborném periodiku
Časopis / Zdroj	Chemistry - A European Journal
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202100895
Doi	http://dx.doi.org/10.1002/chem.202100895
Klíčová slova	CD spectroscopy; DNA quadruplexes; G-quartets; nucleic acid folding; molecular dynamics calculations; NMR spectroscopy
Popis	Guanine quadruplexes (G4s) are noncanonical forms of nucleic acids that are frequently found in genomes. The stability of G4s depends, among other factors, on the number of G-tetrads. Three- or four-tetrad G4s and antiparallel two-tetrad G4s have been characterized experimentally; however, the existence of an intramolecular (i. e., not dimeric or multimeric) two-tetrad parallel-stranded DNA G4 has never been experimentally observed. Many sequences compatible with two-tetrad G4 can be found in important genomic regions, such as promoters, for which parallel G4s predominate. Using experimental and theoretical approaches, the propensity of the model sequence AATGGGTGGGTTTGGGTGGGTAA to form an intramolecular parallel-stranded G4 upon increasing the number of GGG-to-GG substitutions has been studied. Deletion of a single G leads to the formation of intramolecular G4s with a stacked G-triad, whose topology depends on the location of the deletion. Removal of another guanine from another G-tract leads to di- or multimeric G4s. Further deletions mostly prevent the formation of any stable G4. Thus, a solitary two-tetrad parallel DNA G4 is not thermodynamically stable and requires additional interactions through capping residues. However, transiently populated metastable two-tetrad species can associate to form stable dimers, the dynamic formation of which might play additional delicate roles in gene regulation. These findings provide essential information for bioinformatics studies searching for potential G4s in genomes.
Související projekty:	Atomically resolved in vivo NMR spectroscopy as a novel tool for biological testing of therapeutically important genomic non-canonical DNA targets and their interactions with drugs in phenotypically diversified cancer cells.