Chemical basis of DNA sugar-phosphate cleavage by low-energy electrons

J Am Chem Soc. 2005 Nov 30;127(47):16592-8. doi: 10.1021/ja054129q.

Abstract

DNA damage by low-energy electrons (LEE) was examined using a novel system in which thin solid films of oligonucleotide tetramers (CGTA and GCAT) were irradiated with monoenergetic electrons (10 eV) under ultrahigh vacuum. The products of irradiation were examined by HPLC. These analyses permitted the quantitation of 16 nonmodified nucleobase, nucleoside, and nucleotide fragments of each tetramer resulting from the cleavage of phosphodiester and N-glycosidic bonds. The distribution of nonmodified products suggests a mechanism of damage involving initial electron attachment to nucleobase moieties, followed by electron transfer to the sugar-phosphate backbone, and subsequent dissociation of the phosphodiester bond. Moreover, virtually all the nonmodified fragments contained a terminal phosphate group at the site of cleavage. These results demonstrate that the phosphodiester bond breaks by a distinct pathway in which the negative charge localizes on the phosphodiester bond giving rise to nonmodified fragments with an intact phosphate group. Conversely, the radical must localize on the sugar moiety to give as yet unidentified modifications. In summary, the reaction of LEE with simple tetramers involved dissociative electron attachment leading to phosphodiester bond cleavage and the formation of nonmodified fragments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • DNA / chemistry*
  • DNA / radiation effects*
  • DNA Damage*
  • Electrons*
  • Oligonucleotides / chemistry
  • Oligonucleotides / radiation effects
  • Sugar Phosphates / chemistry*
  • Sugar Phosphates / radiation effects*

Substances

  • Oligonucleotides
  • Sugar Phosphates
  • DNA