DNA stability

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Although DNA is generally viewed as a stable molecule, many conditions can cause loss of DNA bases or strand breakage.


  • Depurination involves the loss of purine bases forming abasic sites
  • Depurination is one of the two limiting factors in chemical synthesis of long DNA oligos (the other is coupling efficiency)
  • DNA under physiological conditions has been estimated to depurinate at a rate of [math]3\cdot 10^{-11}[/math]/sec at 37C and pH 7.4 [1]
  • Heating DNA for 10m@100 at pH 7.0 leads to about 1 apurinic site per 1000 base pairs
  • The activation energy of depurination is around 29 kcal/mol
  • Higher temperatures lead to faster depurination
  • Denatured DNA depurinates at about 4 times the rate of dsDNA @ pH 7.4
  • Methylated As (6-methyladenine) found in bacteria are depurinated 4 times faster than the unmethylated purine bases
  • Depurination decreases at higher pH (thus acidic conditions favor depurination)
  • Depurination proceeds more rapidly in buffers of low ionic strength
  • Depurination is correlated with lower transformation efficiency
  • Depurination is independent of sequence


  • Cytosine can be spontaneously deaminated to form uracil.

Strand cleavage

  • Abasic sites are alkali-labile. Under mildly alkaline conditions, β-elimination occurs which nicks 3' to the abasic site leaving a 5'-P on the downstream fragment
  • Under strong alkaline conditions, δ-elimination will occur after β-elimination which completely removes the abasic site leaving a 3'-P on the upstream fragment and a 5'-P on the downstream fragment


  1. Lindahl T and Nyberg B. Rate of depurination of native deoxyribonucleic acid. Biochemistry. 1972 Sep 12;11(19):3610-8. PubMed ID:4626532 | HubMed [lindahl72]
  2. Frederico LA, Kunkel TA, and Shaw BR. Cytosine deamination in mismatched base pairs. Biochemistry. 1993 Jul 6;32(26):6523-30. PubMed ID:8329382 | HubMed [frederico93]

All Medline abstracts: PubMed | HubMed