Hydrolysis of N3-methyl-2′-deoxycytidine: Model compound for reactivity of protonated cytosine residues in DNA

Lawrence Sowers, W. David Sedwick, Barbara Ramsay Shaw

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Protonation of cytosine residues at physiological pH may occur in DNA as a consequence of both alkylation and aberrant base-pair formation. When cytosine derivatives are protonated, they undergo hydrolysis reactions at elevated rates and can either deaminate to form the corresponding uracil derivatives or depyrimidinate generating abasic sites. The kinetic parameters for reaction of protonated cytosine are derived by studying the hydrolysis of N3-methyl-2′-deoxycytidine (m3dC), a cytosine analogue which is predominantly protonated at physiological pH. Both deamination and depyrimidimation reaction rates are shown to be linearly dependent upon the fraction of protonated molecules. We present here thermodynamic parameters which allow determination of hydrolysis rates of m3dC as functions of pH and temperature. Protonation of cytosine residues in DNA, as induced by aberrant base-pair formation or base modification, may accelerate the rate of both deamination and depyrimidation up to several thousand-fold under physiological conditions.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume215
Issue number1
DOIs
StatePublished - 1989
Externally publishedYes

Fingerprint

Deoxycytidine
Cytosine
Hydrolysis
DNA
Deamination
Base Pairing
Uracil
Alkylation
Thermodynamics
Temperature

Keywords

  • Cytosine residues, protonation
  • Deamination reaction rates
  • Depyrimidination reaction rates
  • DNA
  • N-Methyl-2′-deoxycytidine
  • protonated cytosine residues
  • Protonated cytosine residues

ASJC Scopus subject areas

  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Hydrolysis of N3-methyl-2′-deoxycytidine : Model compound for reactivity of protonated cytosine residues in DNA. / Sowers, Lawrence; David Sedwick, W.; Shaw, Barbara Ramsay.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 215, No. 1, 1989, p. 131-138.

Research output: Contribution to journalArticle

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N2 - Protonation of cytosine residues at physiological pH may occur in DNA as a consequence of both alkylation and aberrant base-pair formation. When cytosine derivatives are protonated, they undergo hydrolysis reactions at elevated rates and can either deaminate to form the corresponding uracil derivatives or depyrimidinate generating abasic sites. The kinetic parameters for reaction of protonated cytosine are derived by studying the hydrolysis of N3-methyl-2′-deoxycytidine (m3dC), a cytosine analogue which is predominantly protonated at physiological pH. Both deamination and depyrimidimation reaction rates are shown to be linearly dependent upon the fraction of protonated molecules. We present here thermodynamic parameters which allow determination of hydrolysis rates of m3dC as functions of pH and temperature. Protonation of cytosine residues in DNA, as induced by aberrant base-pair formation or base modification, may accelerate the rate of both deamination and depyrimidation up to several thousand-fold under physiological conditions.

AB - Protonation of cytosine residues at physiological pH may occur in DNA as a consequence of both alkylation and aberrant base-pair formation. When cytosine derivatives are protonated, they undergo hydrolysis reactions at elevated rates and can either deaminate to form the corresponding uracil derivatives or depyrimidinate generating abasic sites. The kinetic parameters for reaction of protonated cytosine are derived by studying the hydrolysis of N3-methyl-2′-deoxycytidine (m3dC), a cytosine analogue which is predominantly protonated at physiological pH. Both deamination and depyrimidimation reaction rates are shown to be linearly dependent upon the fraction of protonated molecules. We present here thermodynamic parameters which allow determination of hydrolysis rates of m3dC as functions of pH and temperature. Protonation of cytosine residues in DNA, as induced by aberrant base-pair formation or base modification, may accelerate the rate of both deamination and depyrimidation up to several thousand-fold under physiological conditions.

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