Conformational profiling of a G-rich sequence within the c-KIT promoter

Conformational profiling of a G-rich sequence within the c-KIT promoter. Rigo, R., Dean, W. L., Gray, R. D., Chaires, J. B., & Sissi, C. Nucleic Acids Research, 45(22):13056–13067, December, 2017. tex.ids= rigoConformationalProfilingGrich2017 publisher: Oxford University Press

Paper doi abstract bibtex

G-quadruplexes (G4) within oncogene promoters are considered to be promising anticancer targets. However, often they undergo complex structural rearrangements that preclude a precise description of the optimal target. Moreover, even when solved structures are available, they refer to the thermodynamically stable forms but little or no information is supplied about their complex multistep folding pathway. To shed light on this issue, we systematically followed the kinetic behavior of a G-rich sequence located within the c-KIT proximal promoter (kit2) in the presence of monovalent cations K + and Na + . A very short-lived intermediate was observed to start the G4 folding process in both salt conditions. Subsequently, the two pathways diverge to produce distinct thermodynamically stable species (parallel and antiparallel G-quadruplex in K + and Na + , respectively). Remarkably, in K + -containing solution a branched pathway is required to drive the wild type sequence to distribute between a monomeric and dimeric G-quadruplex. Our approach has allowed us to identify transient forms whose relative abundance is regulated by the environment; some of them were characterized by a half-life within the timescale of physiological DNA processing events and thus may represent possible unexpected targets for ligands recognition.

@article{Rigo2017,
	title = {Conformational profiling of a {G}-rich sequence within the c-{KIT} promoter},
	volume = {45},
	issn = {0305-1048},
	url = {http://academic.oup.com/nar/article/45/22/13056/4561654},
	doi = {10.1093/nar/gkx983},
	abstract = {G-quadruplexes (G4) within oncogene promoters are considered to be promising anticancer targets. However, often they undergo complex structural rearrangements that preclude a precise description of the optimal target. Moreover, even when solved structures are available, they refer to the thermodynamically stable forms but little or no information is supplied about their complex multistep folding pathway. To shed light on this issue, we systematically followed the kinetic behavior of a G-rich sequence located within the c-KIT proximal promoter (kit2) in the presence of monovalent cations K + and Na + . A very short-lived intermediate was observed to start the G4 folding process in both salt conditions. Subsequently, the two pathways diverge to produce distinct thermodynamically stable species (parallel and antiparallel G-quadruplex in K + and Na + , respectively). Remarkably, in K + -containing solution a branched pathway is required to drive the wild type sequence to distribute between a monomeric and dimeric G-quadruplex. Our approach has allowed us to identify transient forms whose relative abundance is regulated by the environment; some of them were characterized by a half-life within the timescale of physiological DNA processing events and thus may represent possible unexpected targets for ligands recognition.},
	number = {22},
	journal = {Nucleic Acids Research},
	author = {Rigo, Riccardo and Dean, William L. and Gray, Robert D. and Chaires, Jonathan B. and Sissi, Claudia},
	month = dec,
	year = {2017},
	pmid = {29069417},
	note = {tex.ids= rigoConformationalProfilingGrich2017
publisher: Oxford University Press},
	pages = {13056--13067},
}

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