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Nucleic Acids Research Advance Access originally published online on September 6, 2008
Nucleic Acids Research 2008 36(18):5750-5762; doi:10.1093/nar/gkn553
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Nucleic Acids Research, 2008, Vol. 36, No. 18 5750-5762
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

RAG2's non-core domain contributes to the ordered regulation of V(D)J recombination

John D. Curry and Mark S. Schlissel*

Division of Immunology, Department of Molecular and Cell Biology, University of California at Berkeley, 439 Life Sciences Addition, Berkeley, CA 94720-3200, USA

*To whom correspondence should be addressed. Tel: +1 510 643 2462; Fax: +1 510 642 6845; Email: mss{at}berkeley.edu

Received July 29, 2008. Revised August 13, 2008. Accepted August 13, 2008.

Variable (diversity) joining [V(D)J] recombination of immune gene loci proceeds in an ordered manner with D to J portions recombining first and then an upstream V joins that recombinant. We present evidence that the non-core domain of recombination activating gene (RAG) protein 2 is involved in the regulation of recombinatorial order. In mice lacking the non-core domain of RAG2 the ordered rearrangement is disturbed and direct V to D rearrangements are 10- to 1000-times increased in tri-partite immune gene loci. Some forms of inter-chromosomal translocations between TCRβ and TCR{delta} D gene segments are also increased in the core RAG2 animals as compared with their wild-type (WT) counterparts. In addition, the concise use of proper recombination signal sequences (RSSs) appears to be disturbed in the core RAG2 mice as compared with WT RAG2 animals.


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