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

Sandro Santagata, Eva Besmer, Anna Villa, Fabio Bozzi, John S. Allingham, Cristina Sobacchi, David B. Haniford, Paolo Vezzoni, Michel C. Nussenzweig, Zhen Qiang Pan, Patricia Cortes

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)935-947
Number of pages13
JournalMolecular Cell
Volume4
Issue number6
Publication statusPublished - Dec 1999

ASJC Scopus subject areas

  • Molecular Biology

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  • Cite this

    Santagata, S., Besmer, E., Villa, A., Bozzi, F., Allingham, J. S., Sobacchi, C., Haniford, D. B., Vezzoni, P., Nussenzweig, M. C., Pan, Z. Q., & Cortes, P. (1999). The RAG1/RAG2 complex constitutes a 3' flap endonuclease: Implications for junctional diversity in V(D)J and transpositional recombination. Molecular Cell, 4(6), 935-947.