Non-enzymatic depurination of nucleic acids: factors and mechanisms

PLoS One. 2014 Dec 29;9(12):e115950. doi: 10.1371/journal.pone.0115950. eCollection 2014.

Abstract

Depurination has attracted considerable attention since a long time for it is closely related to the damage and repair of nucleic acids. In the present study, depurination using a pool of 30-nt short DNA pieces with various sequences at diverse pH values was analyzed by High Performance Liquid Chromatography (HPLC). Kinetic analysis results showed that non-enzymatic depurination of oligodeoxynucleotides exhibited typical first-order kinetics, and its temperature dependence obeyed Arrhenius' law very well. Our results also clearly showed that the linear relationship between the logarithms of rate constants and pH values had a salient point around pH 2.5. Interestingly and unexpectedly, depurination depended greatly on the DNA sequences. The depurination of poly (dA) was found to be extremely slow, and thymine rich sequences depurinated faster than other sequences. These results could be explained to some extent by the protonation of nucleotide bases. Moreover, two equations were obtained based on our data for predicting the rate of depurination under various conditions. These results provide basic data for gene mutagenesis and nucleic acids metabolism in acidic gastric juice and some acidic organelles, and may also help to rectify some misconceptions about depurination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromatography, High Pressure Liquid
  • DNA / metabolism
  • Hydrogen-Ion Concentration
  • Kinetics
  • Nucleic Acids / metabolism*
  • Oligodeoxyribonucleotides / metabolism
  • Protons
  • Purines / metabolism*
  • Salts / chemistry
  • Temperature
  • Time Factors

Substances

  • Nucleic Acids
  • Oligodeoxyribonucleotides
  • Protons
  • Purines
  • Salts
  • DNA

Grant support

This work was supported by “Fund for Distinguished Young Scholars” of Shandong province [JQ201204], Program for Changjiang Scholars and Innovative Research Team in University [IRT1188], and “National Youth Qianren Plan.” Funding for open access charge: “Fund for Distinguished Young Scholars” of Shandong province [JQ201204]; http://www.sdnsf.gov.cn/portal/. XL is the author who received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.