RAG2's non-core domain contributes to the ordered regulation of V(D)J recombination.
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 TCRbeta and TCRdelta 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.
Curry
John D
JD
Division of Immunology, Department of Molecular and Cell Biology, University of California at Berkeley, 439 Life Sciences Addition, Berkeley, CA 94720-3200, USA.
Schlissel
Mark S
MS
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D051379:Mice; D009154:Mutation; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
D004268:DNA-Binding Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; C499308:Rag2 protein, mouse
Immunity. 1996 Dec;5(6):575-89
8986717
EMBO J. 1984 Jun;3(6):1209-19
6086308
J Exp Med. 2007 Oct 1;204(10):2293-303
17785508
Immunity. 2007 Oct;27(4):561-71
17936034
Science. 1993 May 14;260(5110):953-9
8493533
Nature. 2007 Dec 13;450(7172):1106-10
18033247
Genes Dev. 1998 Aug 1;12(15):2305-17
9694796
Immunity. 2002 Nov;17(5):639-51
12433370
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1209-14
12531919
J Immunol. 1996 Nov 1;157(9):4005-15
8892634
Mol Cell Biol. 2002 Nov;22(22):7790-801
12391148
DNA Repair (Amst). 2006 Sep 8;5(9-10):1246-58
16798110
Immunity. 2005 Aug;23(2):203-12
16111638
Mol Cell Biol. 2002 Jan;22(1):69-77
11739723
Genes Dev. 1993 Dec;7(12B):2520-32
8276236
EMBO J. 2003 Apr 15;22(8):1922-30
12682024
J Exp Med. 1997 Feb 17;185(4):609-20
9034140
Nature. 1983 Apr 14;302(5909):575-81
6300689
Nature. 1992 Nov 19;360(6401):225-31
1359428
Mol Cell. 2001 Dec;8(6):1383-90
11779512
Nucleic Acids Res. 1994 May 25;22(10):1805-9
8208603
Nucleic Acids Res. 1994 May 25;22(10):1810-4
8208604
Annu Rev Immunol. 2000;18:495-527
10837067
Nucleic Acids Res. 2004 Aug 24;32(15):4539-49
15328366