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Las secuencias prevalentes en el genoma humano pueden formar estructuras de mini i-motif a pH fisiológico

Bartomeu Mir^1,2, Israel Serrano³, Diana Buitrago⁴

¹Inorganic and Organic Chemistry Department, Organic Chemistry Section, and IBUB, University of Barcelona , Martí i Franquès 1-11, 08028 Barcelona, Spain.

Journal of the American Chemical Society

|September 22, 2017

Resumen

Las secuencias repetitivas de ADN forman estructuras cuádruples tipo i-motif a pH fisiológico, estabilizadas por pares de bases únicos. Estas estructuras son comunes en el genoma humano y se encuentran en los genes relacionados con el desarrollo.

Área de la Ciencia:

La bioquímica
Biología estructural
La genómica

Sus antecedentes:

Las secuencias repetitivas de ADN son cada vez más reconocidas por sus funciones más allá de los elementos estructurales simples.
Comprender las estructuras de orden superior del ADN es crucial para descifrar la regulación y la función de los genes.
Las secuencias repetitivas específicas pueden adoptar estructuras de ADN no canónicas.

Objetivo del estudio:

Para determinar la estructura de la solución de d ((TCGTTCCGT) y las secuencias repetitivas de ADN relacionadas.
Investigar las bases estructurales para la formación de ADN cuadruplex a pH fisiológico.
Explorar la prevalencia y la función potencial de estas secuencias en el genoma humano.

Principales métodos:

Espectroscopia de resonancia magnética nuclear (RMN) para la determinación de la estructura de la solución.
Análisis bioinformático para la identificación de la prevalencia de secuencias en el genoma humano.
Estudios estructurales dependientes del pH para caracterizar la estabilidad.

Principales resultados:

Varias secuencias repetitivas de ADN se pliegan en cuadruplexos de tipo i-motif a pH fisiológico.
La estructura cuadruplexa está estabilizada por pares de bases C: C + hemiprotonadas y tetradas de ranura menores (G: C o G: T).
Estas estructuras exhiben una alta estabilidad con valores de transición de pH efectivos (pHT) superiores a 7.5, y las secuencias más largas forman estructuras de "perlas de rosario" en tándem.

Conclusiones:

Las secuencias de repetición d ((TCGTTCCGT) y relacionadas forman estructuras cuádruples estables, similares a i-motif.
Estos cuádruplexos están estabilizados por una combinación única de emparejamiento de bases e interacciones tetrádicas.
La prevalencia de estas secuencias en el genoma humano, particularmente en los genes relacionados con el desarrollo, sugiere importantes roles biológicos.

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