Solution equilibria of cytosine- and guanine-rich sequences near the promoter region of the n-myc gene that contain stable hairpins within lateral loops

Cytosine- and guanine-rich regions of DNA are capable of forming complex structures named i-motifs and G-quadruplexes, respectively. In the present study the solution equilibria at nearly physiological conditions of a 34-base long cytosine-rich sequence and its complementary guanine-rich strand corr...

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Vydáno v:	Biochimica et biophysica acta Ročník 1840; číslo 1; s. 41 - 52
Hlavní autoři:	Benabou, Sanae, Ferreira, Rubén, Aviñó, Anna, González, Carlos, Lyonnais, Sébastien, Solà, Maria, Eritja, Ramon, Jaumot, Joaquim, Gargallo, Raimundo
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Netherlands Elsevier B.V 01.01.2014
Témata:	adenine Chromatography Chromatography, Gel Circular Dichroism cytosine Cytosine - chemistry DNA DNA - chemistry DNA - genetics G-quadruplex G-Quadruplexes Guanine - chemistry i-Motif introns mass spectrometry Models, Chemical Multivariate analysis n-myc oncogenes promoter regions Promoter Regions, Genetic Proto-Oncogene Proteins c-myc - chemistry Proto-Oncogene Proteins c-myc - genetics Quadruplex/duplex competition Solutions Spectrometry, Mass, Electrospray Ionization Quadruplex/duplex competition i-Motif n-myc Multivariate analysis Chromatography G-quadruplex
ISSN:	0304-4165, 0006-3002, 1872-8006
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Shrnutí:	Cytosine- and guanine-rich regions of DNA are capable of forming complex structures named i-motifs and G-quadruplexes, respectively. In the present study the solution equilibria at nearly physiological conditions of a 34-base long cytosine-rich sequence and its complementary guanine-rich strand corresponding to the first intron of the n-myc gene were studied. Both sequences, not yet studied, contain a 12-base tract capable of forming stable hairpins inside the i-motif and G-quadruplex structures, respectively. Spectroscopic, mass spectrometry and separation techniques, as well as multivariate data analysis methods, were used to unravel the species and conformations present. The cytosine-rich sequence forms two i-motifs that differ in the protonation of bases located in the loops. A stable Watson–Crick hairpin is formed by the bases in the first loop, stabilizing the i-motif structure. The guanine-rich sequence adopts a parallel G-quadruplex structure that is stable throughout the pH range 3–7, despite the protonation of cytosine and adenine bases at lower pH values. The presence of G-quadruplex aggregates was confirmed using separation techniques. When mixed, G-quadruplex and i-motif coexist with the Watson–Crick duplex across a pH range from approximately 3.0 to 6.5. Two cytosine- and guanine-rich sequences in n-myc gene may form stable i-motif and G-quadruplex structures even in the presence of long loops. pH modulates the equilibria involving the intramolecular structures and the intermolecular Watson–Crick duplex. Watson–Crick hairpins located in the intramolecular G-quadruplexes and i-motifs in the promoter regions of oncogenes could play a role in stabilizing these structures. •Two novel cytosine- and guanine-rich regions at the promoter of the n-myc gene are studied.•Both sequences show unusual long loop which likely forms a stable hairpin structure.•Spectroscopy, chromatography, and multivariate analyses are used.•The formation of i-motif and G-quadruplex is demonstrated.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0304-4165 0006-3002 1872-8006
DOI:	10.1016/j.bbagen.2013.08.028