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.

Contents

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 4\cdot 10^{-9}/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

  1. Lindahl T and Nyberg B. . pmid:4626532. PubMed HubMed [lindahl72]
  2. Frederico LA, Kunkel TA, and Shaw BR. . pmid:8329382. PubMed HubMed [frederico93]
All Medline abstracts: PubMed HubMed
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