Incorporation of zebularine from its 2′-deoxyribonucleoside triphosphate derivative and activity as a template-coding nucleobase

Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) was studied as both a 2 ′-deoxyribosyl 5 ′-triphosphate derivative and as a template incorporated into an oligonucleotide. Using a novel pyrosequencing assay, zebularine acted as cytosine analog and was incorporated into DNA with a templa...

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Detalles Bibliográficos
Autores: Dowd, Casimir L., Sutch, Brian T., Haworth, Ian S., Márquez, Víctor E., Yang, Allen, Eritja Casadellà, Ramón
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2008
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/125040
Acceso en línea:http://hdl.handle.net/10261/125040
Access Level:acceso abierto
Palabra clave:5-azacytidine
zebularine
DNA methylation
Epigenetics
Enzyme Inhibitors
DNA
Descripción
Sumario:Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) was studied as both a 2 ′-deoxyribosyl 5 ′-triphosphate derivative and as a template incorporated into an oligonucleotide. Using a novel pyrosequencing assay, zebularine acted as cytosine analog and was incorporated into DNA with a template pairing profile most similar to cytosine, pairing with greatest efficiency opposite guanine in the template strand. Guanine was incorporated with greater affinity than adenine opposite a zebularine in the template strand. Computer modeling of base-pairing structures supported a better fit of zebularine opposite guanine than adenine. Zebularine acts as a cytosine analog, which supports its activity as an inhibitor of cytosine methyltransferase.