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RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination.

Abstract:The vast repertoire of immunoglobulins and T cell receptors is generated, in part, by V(D)J recombination, a series of genomic rearrangements that occur specifically in developing lymphocytes. The recombination activating gene, RAG-1, which is a gene expressed exclusively in maturing lymphoid cells, was previously isolated. RAG-1 inefficiently induced V(D)J recombinase activity when transfected into fibroblasts, but cotransfection with an adjacent gene, RAG-2, has resulted in at least a 1000-fold increase in the frequency of recombination. The 2.1-kilobase RAG-2 complementary DNA encodes a putative protein of 527 amino acids whose sequence is unrelated to that of RAG-1. Like RAG-1, RAG-2 is conserved between species that carry out V(D)J recombination, and its expression pattern correlates precisely with that of V(D)J recombinase activity. In addition to being located just 8 kilobases apart, these convergently transcribed genes are unusual in that most, if not all, of their coding and 3' untranslated sequences are contained in single exons. RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction.

参考文献

[1]  H. Snodgrass,et al.  Expression of T-cell antigen receptor genes during fetal development in the thymus , 1985, Nature.

[2]  J. Weill,et al.  Rearrangement of a chicken immunoglobulin gene occurs in the lymphoid lineage of transgenic mice , 1987, Nature.

[3]  M. Lieber,et al.  V(D)J recombination: a functional definition of the joining signals. , 1989, Genes & development.

[4]  K. Mizuuchi,et al.  Mechanism of bacteriophage mu transposition. , 1986, Annual review of genetics.

[5]  M. Lieber,et al.  Extrachromosomal DNA substrates in pre-B cells undergo inversion or deletion at immunoglobulin V-(D)-J joining signals , 1987, Cell.

[6]  M. Hacker,et al.  Preparation of lymphocyte-activating factor from continuous murine macrophage cell lines. , 1977, Cellular immunology.

[7]  F. Alt,et al.  Regulated progression of a cultured pre-B-cell line to the B-cell stage , 1985, Nature.

[8]  S. Tonegawa Somatic generation of antibody diversity , 1983, Nature.

[9]  B. Seed An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2 , 1987, Nature.

[10]  David Baltimore,et al.  Organization and reorganization of immunoglobulin genes in A-MuLV-transformed cells: Rearrangement of heavy but not light chain genes , 1981, Cell.

[11]  T. Honjo,et al.  A protein binding to the Jk recombination sequence of immunoglobulin genes contains a sequence related to the integrase motif , 1989, Nature.

[12]  L. Hood,et al.  Introduced T cell receptor variable region gene segments recombine in pre-B cells: Evidence that B and T cells use a common recombinase , 1986, Cell.

[13]  Mark M. Davis,et al.  Expression of genes of the T-cell antigen receptor complex in precursor thymocytes , 1985, Nature.

[14]  B. Franza,et al.  Fos and jun: The AP-1 connection , 1988, Cell.

[15]  F. Alt,et al.  Ordered rearrangement of immunoglobulin heavy chain variable region segments. , 1984, The EMBO journal.

[16]  S. Tonegawa,et al.  Developmental regulation of T-cell receptor gene expression , 1985, Nature.

[17]  A. Landy Dynamic, structural, and regulatory aspects of lambda site-specific recombination. , 1989, Annual review of biochemistry.

[18]  N. Craig The mechanism of conservative site-specific recombination. , 1988, Annual review of genetics.

[19]  M. Lieber,et al.  Developmental stage specificity of the lymphoid V(D)J recombination activity. , 1987, Genes & development.

[20]  L. Guarente,et al.  Yeast HAP2 and HAP3: transcriptional activators in a heteromeric complex. , 1988, Science.

[21]  B. W. Erickson,et al.  Immunoglobulin VH gene structure and diversity in Heterodontus, a phylogenetically primitive shark. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[22]  W. Lamph,et al.  Different genes control the susceptibility of mice to Moloney or Abelson murine leukemia viruses , 1985, Journal of virology.

[23]  Complete nucleotide sequences of three VH genes in Caiman, a phylogenetically ancient reptile: evolutionary diversification in coding segments and variation in the structure and organization of recombination elements. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Schatz,et al.  Stable expression of immunoglobulin gene V(D)J recombinase activity by gene transfer into 3T3 fibroblasts , 1988, Cell.

[25]  J. Weill,et al.  A single rearrangement event generates most of the chicken immunoglobulin light chain diversity , 1985, Cell.

[26]  W. J. Dower,et al.  High efficiency transformation of E. coli by high voltage electroporation , 1988, Nucleic Acids Res..

[27]  G. Lutfalla,et al.  Rearrangement and expression of rabbit immunoglobulin kappa light chain gene in transgenic mice. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[28]  David Baltimore,et al.  The V(D)J recombination activating gene, RAG-1 , 1989, Cell.

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