Hairpin coding end opening is mediated by RAG1 and RAG2 proteins

Eva Besmer, Jorge Mansilla-Soto, Sylvanie Cassard, Dennis J. Sawchuk, Greg Brown, Moshe J. Sadofsky, Susanna M. Lewis, Michel C. Nussenzweig, Patricia Cortes

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Despite the importance of hairpin opening in antigen receptor gene assembly, the molecular machinery that mediates this reaction has not been defined. Here, we show that RAG1 plus RAG2 can open DNA hairpins. Hairpin opening by RAGs is not sequence specific, but in Mg2+, hairpin opening occurs only in the context of a regulated cleavage complex. The chemical mechanism of harpin opening by RAGs resembles RSS cleavage and 3′ end processing by HIV integrase and Mu transposase in that these reactions can proceed through alcoholysis. Mutations in either RAG1 or RAG2 that interfere with RSS cleavage also interfere with hairpin opening, suggesting that RAGs have a single active site that catalyzes several distinct DNA cleavage reactions.

Original languageEnglish (US)
Pages (from-to)817-828
Number of pages12
JournalMolecular Cell
Volume2
Issue number6
StatePublished - Dec 1998
Externally publishedYes

Fingerprint

HIV Integrase
DNA Cleavage
Antigen Receptors
Catalytic Domain
Mutation
DNA
Genes
Proteins
mu transposase

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Besmer, E., Mansilla-Soto, J., Cassard, S., Sawchuk, D. J., Brown, G., Sadofsky, M. J., ... Cortes, P. (1998). Hairpin coding end opening is mediated by RAG1 and RAG2 proteins. Molecular Cell, 2(6), 817-828.

Hairpin coding end opening is mediated by RAG1 and RAG2 proteins. / Besmer, Eva; Mansilla-Soto, Jorge; Cassard, Sylvanie; Sawchuk, Dennis J.; Brown, Greg; Sadofsky, Moshe J.; Lewis, Susanna M.; Nussenzweig, Michel C.; Cortes, Patricia.

In: Molecular Cell, Vol. 2, No. 6, 12.1998, p. 817-828.

Research output: Contribution to journalArticle

Besmer, E, Mansilla-Soto, J, Cassard, S, Sawchuk, DJ, Brown, G, Sadofsky, MJ, Lewis, SM, Nussenzweig, MC & Cortes, P 1998, 'Hairpin coding end opening is mediated by RAG1 and RAG2 proteins', Molecular Cell, vol. 2, no. 6, pp. 817-828.
Besmer E, Mansilla-Soto J, Cassard S, Sawchuk DJ, Brown G, Sadofsky MJ et al. Hairpin coding end opening is mediated by RAG1 and RAG2 proteins. Molecular Cell. 1998 Dec;2(6):817-828.
Besmer, Eva ; Mansilla-Soto, Jorge ; Cassard, Sylvanie ; Sawchuk, Dennis J. ; Brown, Greg ; Sadofsky, Moshe J. ; Lewis, Susanna M. ; Nussenzweig, Michel C. ; Cortes, Patricia. / Hairpin coding end opening is mediated by RAG1 and RAG2 proteins. In: Molecular Cell. 1998 ; Vol. 2, No. 6. pp. 817-828.
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