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The Homeodomain Region of Rag-1 Reveals the Parallel Mechanisms of Bacterial and V(D)J Recombination

Spanopoulou, Eugenia and Zaitseva, Florina and Wang, Fu-Hou and Santagata, Sandro and Baltimore, David and Panayotou, George (1996) The Homeodomain Region of Rag-1 Reveals the Parallel Mechanisms of Bacterial and V(D)J Recombination. Cell, 87 (2). pp. 263-276. ISSN 0092-8674. doi:10.1016/s0092-8674(00)81344-6.

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The V(D)J recombinase subunits Rag-1 and Rag-2 mediate assembly of antigen receptor gene segments. We studied the mechanisms of DNA recognition by Rag-1/Rag-2 using surface plasmon resonance. The critical step for signal recognition is binding of Rag-1 to the nonamer. This is achieved by a region of Rag-1 homologous to the DNA-binding domain of the Hin family of bacterial invertases and to homeodomain proteins. Strikingly, the Hin homeodomain can functionally substitute for the Rag-1 homologous region. Rag-1 also interacts with the heptamer but with low affinity. Rag-2 shows no direct binding to DNA. Once the Rag-1/Rag-2 complex is engaged on the DNA, subsequent cleavage is directed by the heptamer sequence. This order of events remarkably parallels mechanisms that mediate transposition in bacteria and nematodes.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1996 Cell Press. Under an Elsevier user license. Received 18 June 1996, Revised 28 August 1996. Correspondence should be addressed to E. S. The authors would like to thank Dr. Patricia Cortes for valuable suggestions, Dr. Reid Johnson for the Hin clone, Drs. David Schatz and Christopher Roman for critical reading of the manuscript, and Drs. William Farley and Lesley Stolz of Pharmacia for the initial experiments with the BIAcore. E. S. is grateful to Christopher Roman, Patricia Cortes, and Dina Alexandropoulos for their generosity. G. P. would like to thank Mike Waterfield for his support. This work was supported by a Leukemia Research Foundation grant to E. S.
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Leukemia Research FoundationUNSPECIFIED
Issue or Number:2
Record Number:CaltechAUTHORS:20200422-151000513
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Official Citation:Eugenia Spanopoulou, Florina Zaitseva, Fu-Hou Wang, Sandro Santagata, David Baltimore, George Panayotou, The Homeodomain Region of Rag-1 Reveals the Parallel Mechanisms of Bacterial and V(D)J Recombination, Cell, Volume 87, Issue 2, 1996, Pages 263-276, ISSN 0092-8674,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102739
Deposited By: George Porter
Deposited On:22 Apr 2020 22:36
Last Modified:16 Nov 2021 18:15

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