The RAG1/RAG2 complex constitutes a 3' flap endonuclease: implications for junctional diversity in V(D)J and transpositional recombination

Mol Cell. 1999 Dec;4(6):935-47. doi: 10.1016/s1097-2765(00)80223-3.

Abstract

During V(D)J recombination, processing of branched coding end intermediates is essential for generating junctional diversity. Here, we report that the RAG1/ RAG2 recombinase is a 3' flap endonuclease. Substrates of this nuclease activity include various coding end intermediates, suggesting a direct role for RAG1/ RAG2 in generating junctional diversity during V(D)J recombination. Evidence is also provided indicating that site-specific RSS nicking involves RAG1/RAG2-mediated processing of a localized flap-like structure, implying 3' flap nicking in multiple DNA processing reactions. We have also demonstrated that the bacterial transposase Tn10 contains a 3' flap endonuclease activity, suggesting a mechanistic parallel between RAG1/RAG2 and other transposases. Based on these data, we propose that numerous transposases may facilitate genomic evolution by removing single-stranded extensions during the processing of excision site junctions.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • DNA / genetics*
  • DNA-Binding Proteins / genetics*
  • Genetic Variation
  • Homeodomain Proteins / genetics*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins
  • Recombination, Genetic*
  • Transposases / genetics

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • RAG2 protein, human
  • Rag2 protein, mouse
  • V(D)J recombination activating protein 2
  • RAG-1 protein
  • DNA
  • Transposases