2-Aminopurine-induced mutagenesis in T4 bacteriophage: a model relating mutation frequency to 2-aminopurine incorporation in DNA

Proc Natl Acad Sci U S A. 1977 Nov;74(11):4806-10. doi: 10.1073/pnas.74.11.4806.

Abstract

We measured the in vivo incorporation of 2-aminopurine into DNA of T4 bacteriophage allelic for gene 43 (DNA polymerase), mutator (L56), 43+, and antimutator (L141). The magnitude of incorporation (mol/mol of Thy) was 1/1500 in L56, 1/1600 in 43+, and 1/8900 in L141. The incorporation ratio L56:43+:L141 in vivo was equal to that mediated by the purified DNA polymerases of these allelic phages in vitro. A model for 2-aminopurine-induced A-T in equilibrium G-C transitions is discussed. The model is used to predict the magnitudes of replication errors (C mispairing with a template 2-aminopurine) and incorporation errors (2-aminopurine mispairing with a template C) per round of replication and to investigate the asymmetry in 2-aminopurine-induced transitions favoring the A-T leads to G-C pathway over G-C leads to A-T. We suggest that the fidelity of L56 and L141 DNA polymerases exemplifies one-step and two-step editing, respectively.

Publication types

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

MeSH terms

  • 2-Aminopurine / pharmacology*
  • Adenine / analogs & derivatives*
  • Aminopyrine / metabolism
  • Coliphages / drug effects
  • Coliphages / genetics*
  • DNA, Viral / biosynthesis*
  • Models, Biological
  • Mutagens*

Substances

  • DNA, Viral
  • Mutagens
  • Aminopyrine
  • 2-Aminopurine
  • Adenine