Skip to main content
Journal cover image

Protonated base pairs explain the ambiguous pairing properties of O6-methylguanine.

Publication ,  Journal Article
Williams, LD; Shaw, BR
Published in: Proceedings of the National Academy of Sciences of the United States of America
April 1987

The base-pairing interactions of promutagenic O6-methylguanine (O6-MeGua) with cytosine and thymine in deuterated chloroform were investigated by 1H 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. We 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. O6-MeGua was observed to form a hydrogen-bonded mispair with thymine. Whereas O6-MeGua did not form hydrogen bonds with cytosine (via usual, wobble, or unusual tautomeric structures), it did form a 1:1 hydrogen-bonded complex with protonated cytosine. The pairing of unprotonated cytosine in chloroform is thus consistent with the known preference of O6-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.O6-MeGua as compared with thymine.O6-MeGua base pairs [Gaffney, B. L., Markey, L. A. & Jones, R. A. (1984) Biochemistry 23, 5686-5691]. Our observation that cytosine must be protonated in order to pair with O6-MeGua suggests that the cytosine.O6-MeGua base pair in DNA is stabilized by protonation of cytosine. Through this mechanism, methylation at the O6 position of guanine in double-stranded DNA could promote cross-strand deamination of cytosine (or 5-methylcytosine) to produce uracil (or thymine).

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

April 1987

Volume

84

Issue

7

Start / End Page

1779 / 1783

Related Subject Headings

  • Mutagens
  • Molecular Conformation
  • Magnetic Resonance Spectroscopy
  • Indicators and Reagents
  • Hydrogen Bonding
  • Guanosine
  • Guanine
  • Cytidine
  • Base Composition
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Williams, L. D., & Shaw, B. R. (1987). Protonated base pairs explain the ambiguous pairing properties of O6-methylguanine. Proceedings of the National Academy of Sciences of the United States of America, 84(7), 1779–1783. https://doi.org/10.1073/pnas.84.7.1779
Williams, L. D., and B. R. Shaw. “Protonated base pairs explain the ambiguous pairing properties of O6-methylguanine.Proceedings of the National Academy of Sciences of the United States of America 84, no. 7 (April 1987): 1779–83. https://doi.org/10.1073/pnas.84.7.1779.
Williams LD, Shaw BR. Protonated base pairs explain the ambiguous pairing properties of O6-methylguanine. Proceedings of the National Academy of Sciences of the United States of America. 1987 Apr;84(7):1779–83.
Williams, L. D., and B. R. Shaw. “Protonated base pairs explain the ambiguous pairing properties of O6-methylguanine.Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 7, Apr. 1987, pp. 1779–83. Epmc, doi:10.1073/pnas.84.7.1779.
Williams LD, Shaw BR. Protonated base pairs explain the ambiguous pairing properties of O6-methylguanine. Proceedings of the National Academy of Sciences of the United States of America. 1987 Apr;84(7):1779–1783.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

April 1987

Volume

84

Issue

7

Start / End Page

1779 / 1783

Related Subject Headings

  • Mutagens
  • Molecular Conformation
  • Magnetic Resonance Spectroscopy
  • Indicators and Reagents
  • Hydrogen Bonding
  • Guanosine
  • Guanine
  • Cytidine
  • Base Composition