Post-translational activation of non-homologous DNA end-joining in Xenopus oocyte extracts

Eur J Biochem. 1997 Jul 15;247(2):518-25. doi: 10.1111/j.1432-1033.1997.00518.x.

Abstract

We have analysed the recircularisation of plasmid DNA, cut with two different endonucleases to generate non-homologous DNA ends, in extracts of unfertilised eggs and oocytes of Xenopus. We found that the capacity to join non-homologous DNA ends, generating diagnostic covalently closed monomer circles, appeared during oocyte maturation at the time of germinal vesicle breakdown. This enzyme function was post-translationally activated in oocyte extracts incubated with unfertilised egg extract containing active cdc2/cyclin B, or by incubation with purified cdc2/cyclin B. Dephosphorylation of egg proteins by alkaline phosphatase inhibited the ability to join non-homologous DNA ends. We show that most linear non-homologous DNA ends repaired to form closed-circular supercoiled monomers, are joined without loss of nucleotides. Following partial purification, the activity was inhibited by inhibitors of poly(ADP-Rib) polymerase, an enzyme that is inactive in oocytes, but phosphorylated and activated during maturation. Competitive inhibition of poly(ADP-Rib) polymerase by > 50 microM 3-aminobenzamide prevented the joining of both matched and non-homologous DNA ends. We conclude that post-translational phosphorylation provides one route by which end-joining of non-homologous DNA can be regulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Benzamides / pharmacology
  • CDC2 Protein Kinase / metabolism
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / metabolism
  • DNA Ligase ATP
  • DNA Ligases / metabolism*
  • Embryo, Nonmammalian / metabolism
  • Female
  • Oligodeoxyribonucleotides / chemistry
  • Oligodeoxyribonucleotides / metabolism
  • Oocytes / physiology*
  • Ovum / physiology
  • Phosphorylation
  • Plasmids / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein Processing, Post-Translational*
  • Templates, Genetic
  • Tissue Extracts / metabolism
  • Xenopus laevis

Substances

  • Benzamides
  • Cyclins
  • Oligodeoxyribonucleotides
  • Tissue Extracts
  • 3-aminobenzamide
  • Poly(ADP-ribose) Polymerases
  • CDC2 Protein Kinase
  • Cyclin-Dependent Kinases
  • DNA Ligases
  • DNA Ligase ATP