Protonated base pairs explain the ambiguous pairing properties of O/sup 6/-methylguanine

Journal Article · Wed Apr 01 00:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.7.1779· OSTI ID:6025159

Williams, L D; Shaw, B R

The base-pairing interactions of promutagenic O/sup 6/-methylguanine (O/sup 6/-MeGua) with cytosine and thymine in deuterated chloroform were investigated by /sup 1/H NMR spectroscopy. Nucleosides were derivatized at hydroxyl positions with triisopropylsilyl groups to obtain solubility in nonaqueous solvents and to prevent the ribose hydroxyls from forming hydrogen bonds. The authors were able to observe hydrogen-bonding interactions between nucleic acid bases in a solvent of low dielectric constant, a condition that approximates the hydrophobic interior of the DNA helix. O/sup 6/-MeGua was observed to form a hydrogen-bonded mispair with thymine. The pairing of unprotonated cytosine in chloroform is consistent with the known preference of O/sup 6/-MeGua for thymine over cytosine in polymerase reactions. In contrast, the pairing of protonated cytosine is consistent with the greater stability of oligonucleotide duplexes containing cytosine-O/sup 6/-MeGua as compared with thymine-O/sup 6/-MeGua base pairs. The observation that cytosine must be protonated in order to pair with O/sup 6/-MeGua suggests that the cytosine-O/sup 6/-MeGua base pair in DNA is stabilized by protonation of cytosine. Through this mechanism, methylation at the O/sup 6/ position of guanine in double-stranded DNA could promote cross-strand deamination of cytosine (or 5 methylcytosine) to produce uracil (or thymine).

• Research Organization: Duke Univ., Durham, NC
• OSTI ID: 6025159
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:7
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
DNA ADDUCTS
MOLECULAR STRUCTURE
GUANINE
METHYLATION
NUCLEOSIDES
NUCLEAR MAGNETIC RESONANCE
AMINES
CHEMICAL BONDS
CHLOROFORM
CYTOSINE
DEUTERIUM COMPOUNDS
DNA REPAIR
MUTAGENESIS
NMR SPECTRA
PROTONS
THYMINE
ADDUCTS
AROMATICS
AZAARENES
AZINES
BARYONS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CHEMICAL REACTIONS
CHLORINATED ALIPHATIC HYDROCARBONS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HALOGENATED ALIPHATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
MAGNETIC RESONANCE
NUCLEONS
NUCLEOTIDES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PURINES
PYRIMIDINES
RECOVERY
REPAIR
RESONANCE
RIBOSIDES
SPECTRA
URACILS
550601* - Medicine- Unsealed Radionuclides in Diagnostics