title: Incorporation of zebularine from its 2'-deoxyribonucleoside triphosphate derivative and activity as a template-coding nucleobase.
abstract: Zebularine (1-(beta-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.
authors.affiliation: Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Casimir L
authors.initials: CL
authors.lastname: Dowd
authors.forename: Brian T
authors.initials: BT
authors.lastname: Sutch
authors.forename: Ian S
authors.initials: IS
authors.lastname: Haworth
authors.forename: Ramón
authors.initials: R
authors.lastname: Eritja
authors.forename: Victor E
authors.initials: VE
authors.lastname: Marquez
authors.forename: Allen S
authors.initials: AS
authors.lastname: Yang
mesh_terms: D020029:Base Pairing; D003562:Cytidine / Q000031:analogs & derivatives* / Q000737:chemistry; D015257:DNA-Cytosine Methylases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside; D015257:DNA-Cytosine Methylases