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
- 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 found to depurinate at a rate of [math]\displaystyle{ 4\cdot 10^{-9} }[/math]/sec at 70C and pH 7.4 [1].
Deamination
- 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
References
- Lindahl T and Nyberg B. Rate of depurination of native deoxyribonucleic acid. Biochemistry. 1972 Sep 12;11(19):3610-8. DOI:10.1021/bi00769a018 |
- Frederico LA, Kunkel TA, and Shaw BR. Cytosine deamination in mismatched base pairs. Biochemistry. 1993 Jul 6;32(26):6523-30. DOI:10.1021/bi00077a005 |
