Incorporation of zebularine from its 2'-deoxyribonucleoside triphosphate derivative and activity as a template-coding nucleobase.
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.
Dowd
Casimir L
CL
Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Sutch
Brian T
BT
Haworth
Ian S
IS
Eritja
Ramón
R
Marquez
Victor E
VE
Yang
Allen S
AS
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
D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside; D015257:DNA-Cytosine Methylases