Effect of in vitro cleavage of apurinic/apyrimidinic sites on bleomycin-induced mutagenesis of repackaged lambda phage

Mutat Res. 1990 Feb;240(2):93-100. doi: 10.1016/0165-1218(90)90012-q.

Abstract

Previous studies have revealed bleomycin to be a potent base-substitution mutagen in repackaged phage lambda. In order to assess the role of apurinic/apyrimidinic (AP) sites in bleomycin-induced mutagenesis, bleomycin-damaged lambda DNA was treated with putrescine or endonuclease IV to effect cleavage of bleomycin-induced AP sites. The DNA was then packaged, the phage grown in SOS-induced E. coli, and the frequency of clear-plaque mutants in the progeny was determined. Bleomycin-induced mutagenesis was decreased approx. 2-fold by treating the DNA with putrescine, but was unaffected by endonuclease IV. The results are consistent with the production of bleomycin-induced mutation at certain AP sites having a closely opposed single-strand break, since such sites are cleaved by putrescine but not by endonuclease IV.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacteriophage lambda / drug effects
  • Bacteriophage lambda / genetics
  • Base Composition
  • Bleomycin / metabolism
  • Bleomycin / toxicity*
  • DNA, Viral / drug effects*
  • DNA, Viral / metabolism
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Deoxyribonuclease IV (Phage T4-Induced)
  • Electrophoresis, Agar Gel
  • Endodeoxyribonucleases / pharmacology
  • Mutagenicity Tests
  • Mutagens / pharmacology*
  • Plasmids / genetics
  • Putrescine / pharmacology

Substances

  • DNA, Viral
  • Mutagens
  • Bleomycin
  • Endodeoxyribonucleases
  • Deoxyribonuclease IV (Phage T4-Induced)
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Putrescine