Base-pair induced shifts in the tautomeric equilibrium of a modified DNA base.
We have examined the base-pairing properties of N4-methoxycytosine (mo4C), a mutagenic base analog, in DNA by nuclear magnetic resonance spectroscopy. Unlike standard bases, the tautomeric equilibrium of mo4C could be strongly influenced by base-pair formation. Paired with A, mo4C is found predominantly in the imino configuration in Watson-Crick geometry. However, when paired with G, two structurally distinct configurations are observed in equilibrium with one another. In one configuration, mo4C is in the amino form paired with G in Watson-Crick geometry. In the second species, mo4C is in the imino configuration paired with G in a wobble geometry. This is the first demonstration of basepair induced tautomeric shifts in DNA and supports the hypothesis that rare tautomeric forms may be involved in mutagenesis.
Fazakerley
G V
GV
Département de Biologie Cellulaire et Moléculaire, Centre d'Etudes de Sacaly, Gif-sur-Yvette, France.
Gdaniec
Z
Z
Sowers
L C
LC
D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006860:Hydrogen Bonding; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D009838:Oligodeoxyribonucleotides / Q000737:chemistry
D009838:Oligodeoxyribonucleotides; C036689:N(4)-methoxycytosine; D003596:Cytosine