rag 1 genes


Summary: Genes involved in activating the enzyme VDJ recombinase. RAG-1 is located on chromosome 11 in humans (chromosome 2 in mice) and is expressed exclusively in maturing lymphocytes.

Top Publications

  1. Zarrin A, Fong I, Malkin L, Marsden P, Berinstein N. Cloning and characterization of the human recombination activating gene 1 (RAG1) and RAG2 promoter regions. J Immunol. 1997;159:4382-94 pubmed
    ..Promoter regions of human RAG1 and RAG2 are active in both lymphoid and nonlymphoid cell lines, suggesting that an outside regulatory element is probably involved in the tissue-specific transcriptional regulation of the RAG genes. ..
  2. Goebel P, Janney N, Valenzuela J, Romanow W, Murre C, Feeney A. Localized gene-specific induction of accessibility to V(D)J recombination induced by E2A and early B cell factor in nonlymphoid cells. J Exp Med. 2001;194:645-56 pubmed
    ..We propose that accessibility occurs in a local manner, and that binding sites for factors facilitating accessibility are therefore likely to be associated with individual gene segments. ..
  3. Hikida M, Mori M, Takai T, Tomochika K, Hamatani K, Ohmori H. Reexpression of RAG-1 and RAG-2 genes in activated mature mouse B cells. Science. 1996;274:2092-4 pubmed
    ..These findings suggest that RAG gene products play a heretofore unsuspected role in mature B cells. ..
  4. Bas A, Hammarström S, Hammarström M. Extrathymic TCR gene rearrangement in human small intestine: identification of new splice forms of recombination activating gene-1 mRNA with selective tissue expression. J Immunol. 2003;171:3359-71 pubmed
    ..This seems to be achieved by two parallel processes, extrathymic T cell development and peripheral Ag-driven TCR editing. ..
  5. Fuller K, Storb U. Identification and characterization of the murine Rag1 promoter. Mol Immunol. 1997;34:939-54 pubmed
    ..These findings are discussed with respect to B-cell development and regulation of differential Rag expression by the promoter in pre-B, pre-T, and CNS cells. ..
  6. Muegge K, Vila M, Durum S. Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor beta gene. Science. 1993;261:93-5 pubmed
    ..These data implicate IL-7, a cytokine that is abundantly expressed in embryonic thymus, in driving gene rearrangement during early T cell development. ..
  7. Venkatesh B, Erdmann M, Brenner S. Molecular synapomorphies resolve evolutionary relationships of extant jawed vertebrates. Proc Natl Acad Sci U S A. 2001;98:11382-7 pubmed publisher
    ..Our study also provides molecular evidence to support the monophyly of living tetrapods and teleosts...
  8. Sadofsky M, Hesse J, McBlane J, Gellert M. Expression and V(D)J recombination activity of mutated RAG-1 proteins. Nucleic Acids Res. 1993;21:5644-50 pubmed
    ..Transport of RAG-1 protein to the nucleus was found even with the most extensive deletions studied. The functionality of the deleted proteins is discussed with relation to an alignment of RAG-1 sequences from five animal species. ..
  9. Hsu L, Lauring J, Liang H, Greenbaum S, Cado D, Zhuang Y, et al. A conserved transcriptional enhancer regulates RAG gene expression in developing B cells. Immunity. 2003;19:105-17 pubmed
    ..These findings lead us to conclude that RAG transcription is regulated by distinct elements in developing B and T cells and that Erag is required for optimal levels of RAG expression in early B cell precursors but not in T cells. ..

More Information


  1. Smith J, Grizot S, Arnould S, Duclert A, Epinat J, Chames P, et al. A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences. Nucleic Acids Res. 2006;34:e149 pubmed
    ..These results demonstrate that the plasticity of LAGLIDADG endonucleases allows extensive engineering, and provide a general method to create novel endonucleases with tailored specificities. ..
  2. Groth J, Barrowclough G. Basal divergences in birds and the phylogenetic utility of the nuclear RAG-1 gene. Mol Phylogenet Evol. 1999;12:115-23 pubmed
    ..However, RAG-1 does not evolve in a clocklike manner, suggesting that this gene cannot easily be used for estimating ages of ancient lineages. ..
  3. Tsai C, Drejer A, Schatz D. Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination. Genes Dev. 2002;16:1934-49 pubmed
    ..Our results suggest that the RAG proteins have an architectural function in facilitating proper and efficient V(D)J joining, and a protective function in preventing degradation of broken ends prior to joining. ..
  4. Gellert M. V(D)J recombination: RAG proteins, repair factors, and regulation. Annu Rev Biochem. 2002;71:101-32 pubmed
    ..This transposition helps to explain the mechanism of RAG action and supports earlier proposals that V(D)J recombination evolved from an ancient mobile DNA element. ..
  5. Lambolez F, Azogui O, Joret A, Garcia C, von Boehmer H, Di Santo J, et al. Characterization of T cell differentiation in the murine gut. J Exp Med. 2002;195:437-49 pubmed
    ..Finally, only 3% of CP cells were clearly involved in T cell differentiation, suggesting that these structures may have additional physiological roles in the gut. ..
  6. Maraskovsky E, O Reilly L, Teepe M, Corcoran L, Peschon J, Strasser A. Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice. Cell. 1997;89:1011-9 pubmed
    ..These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2. ..
  7. McBlane J, van Gent D, Ramsden D, Romeo C, Cuomo C, Gellert M, et al. Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell. 1995;83:387-95 pubmed
    ..The hairpin is made as a direct consequence of the cleavage mechanism. Nicking and hairpin formation each require the presence of a signal sequence and both RAG proteins. ..
  8. Spanopoulou E, Roman C, Corcoran L, Schlissel M, Silver D, Nemazee D, et al. Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice. Genes Dev. 1994;8:1030-42 pubmed
    ..These data also support the hypothesis that Rag-1 directly participates in the V(D)J recombination process. ..
  9. Mombaerts P, Clarke A, Rudnicki M, Iacomini J, Itohara S, Lafaille J, et al. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. Nature. 1992;360:225-31 pubmed
    ..TCR-alpha is irrelevant in these developmental processes. The development of gamma delta T cells does not depend on either TCR-alpha or TCR-beta. ..
  10. Ardouin L, Ismaili J, Malissen B, Malissen M. The CD3-gammadeltaepsilon and CD3-zeta/eta modules are each essential for allelic exclusion at the T cell receptor beta locus but are both dispensable for the initiation of V to (D)J recombination at the T cell receptor-beta, -gamma, and -delta loci. J Exp Med. 1998;187:105-16 pubmed
    ..Thus, the CD3 components are differentially involved in the sequential events that make the TCR-beta locus first accessible to, and later insulated from, the action of the V(D)J recombinase. ..
  11. Yu W, Misulovin Z, Suh H, Hardy R, Jankovic M, Yannoutsos N, et al. Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5' of RAG2. Science. 1999;285:1080-4 pubmed
    ..This observation suggests a mechanism by which asymmetrically disposed cis DNA elements could influence the expression of the primordial transposon and thereby capture RAGs for vertebrate evolution. ..
  12. Roman C, Cherry S, Baltimore D. Complementation of V(D)J recombination deficiency in RAG-1(-/-) B cells reveals a requirement for novel elements in the N-terminus of RAG-1. Immunity. 1997;7:13-24 pubmed
    ..Our data suggest that the RAG-1 N-terminus enhances the formation of an active recombination complex that facilitates the rearrangement process. ..
  13. Pâques F, Duchateau P. Meganucleases and DNA double-strand break-induced recombination: perspectives for gene therapy. Curr Gene Ther. 2007;7:49-66 pubmed
    ..Finally, we will discuss the main issues that will need to be addressed in order to bring this promising technology to the patient. ..
  14. Szabo P, Shen S, Telford W, Weksler M. Impaired rearrangement of IgH V to DJ segments in bone marrow Pro-B cells from old mice. Cell Immunol. 2003;222:78-87 pubmed
    ..These data are consistent with the view that impaired V to DJ rearrangement contributes to the decreased levels of bone marrow Pre-B cells as well as the decreased levels of transitional B cells in the periphery. ..
  15. Ait Azzouzene D, Verkoczy L, Peters J, Gavin A, Skog P, VELA J, et al. An immunoglobulin C kappa-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system. J Exp Med. 2005;201:817-28 pubmed
    ..We also demonstrate the unique advantages of our model in the genetic and cellular analysis of immune tolerance. ..
  16. Li J, Iwanami N, Hoa V, Furutani Seiki M, Takahama Y. Noninvasive intravital imaging of thymocyte dynamics in medaka. J Immunol. 2007;179:1605-15 pubmed
    ..Thus, transgenic medaka enables real-time intravital imaging of thymocytes without surgical invasion. ..
  17. Jasinski J, Yu L, Nakayama M, Li M, Lipes M, Eisenbarth G, et al. Transgenic insulin (B:9-23) T-cell receptor mice develop autoimmune diabetes dependent upon RAG genotype, H-2g7 homozygosity, and insulin 2 gene knockout. Diabetes. 2006;55:1978-84 pubmed
    ..scid mouse. The current study demonstrates that the BDC12-4.1 TCR is sufficient to cause diabetes at NOD backcross 1, bypassing polygenic inhibition of insulitis and diabetogenesis. ..
  18. Aidinis V, Plows D, Haralambous S, Armaka M, Papadopoulos P, Kanaki M, et al. Functional analysis of an arthritogenic synovial fibroblast. Arthritis Res Ther. 2003;5:R140-57 pubmed
    ..Our findings support an aggressive role for the SF in the development of the disease and reinforce the perspective of a transformed-like character of the SF. ..
  19. Vaitaitis G, Poulin M, Sanderson R, Haskins K, Wagner D. Cutting edge: CD40-induced expression of recombination activating gene (RAG) 1 and RAG2: a mechanism for the generation of autoaggressive T cells in the periphery. J Immunol. 2003;170:3455-9 pubmed
    ..Therefore, CD40-regulated expression of RAG1 and RAG2 in peripheral T cells may constitute a novel pathway for the generation of autoaggressive T cells. ..
  20. Bentzien F, Struman I, Martini J, Martial J, Weiner R. Expression of the antiangiogenic factor 16K hPRL in human HCT116 colon cancer cells inhibits tumor growth in Rag1(-/-) mice. Cancer Res. 2001;61:7356-62 pubmed
    ..These findings support the potential of 16K hPRL as a therapeutic agent for the treatment of colorectal cancer. ..
  21. Sikes M, Meade A, Tripathi R, Krangel M, Oltz E. Regulation of V(D)J recombination: a dominant role for promoter positioning in gene segment accessibility. Proc Natl Acad Sci U S A. 2002;99:12309-14 pubmed
    ..These spatial constraints on promoter positioning may reflect an RNA polymerase-independent mechanism to target adjacent gene segments for chromatin remodeling events that facilitate rearrangement. ..
  22. Geurgas S, Rodrigues M, Moritz C. The genus Coleodactylus (Sphaerodactylinae, Gekkota) revisited: a molecular phylogenetic perspective. Mol Phylogenet Evol. 2008;49:92-101 pubmed publisher
    ..3+/-4.33 Mya). Most intraspecific cladogenesis occurred through Miocene to Pliocene, and only for two conspecific samples and for C. natalensis could a Quaternary differentiation be assumed (1.9+/-1.3 Mya). ..
  23. Kim K, Bellendir S, Hudson K, Hill C, Hartman G, Hyten D, et al. Fine mapping the soybean aphid resistance gene Rag1 in soybean. Theor Appl Genet. 2010;120:1063-71 pubmed publisher
    ..Several candidate genes for Rag1 are present within the 115-kb interval. The markers identified in this study that are closely linked to Rag1 will be a useful resource in MAS for this important aphid resistance gene. ..
  24. Chen J, Shinkai Y, Young F, Alt F. Probing immune functions in RAG-deficient mice. Curr Opin Immunol. 1994;6:313-9 pubmed
  25. Fleming S, Tsokos G. Complement, natural antibodies, autoantibodies and tissue injury. Autoimmun Rev. 2006;5:89-92 pubmed
    ..Our experiments demonstrate that naturally occurring antibodies and autoantibodies mediate tissue injury only after an organ has been subjected to a stressor such as ischemia. ..
  26. Schuetz C, Huck K, Gudowius S, Megahed M, Feyen O, Hubner B, et al. An immunodeficiency disease with RAG mutations and granulomas. N Engl J Med. 2008;358:2030-8 pubmed publisher
    ..In each case, both parents were heterozygous carriers of a RAG mutation. The mutations were associated with reduced function of RAG in vitro (3 to 30% of normal activity). The parents and one sibling in the three families were healthy. ..
  27. Shoo L, Rose R, Doughty P, Austin J, Melville J. Diversification patterns of pebble-mimic dragons are consistent with historical disruption of important habitat corridors in arid Australia. Mol Phylogenet Evol. 2008;48:528-42 pubmed publisher
    ..Additional genetic structuring in the absence of recognized barriers suggests that an expanded view of potential habitat barriers in the arid zone is required. ..
  28. Munderloh U, Silverman D, MacNamara K, Ahlstrand G, Chatterjee M, Winslow G. Ixodes ovatus Ehrlichia exhibits unique ultrastructural characteristics in mammalian endothelial and tick-derived cells. Ann N Y Acad Sci. 2009;1166:112-9 pubmed publisher
    ..IOE from RF/6A cells, when inoculated into C57BL/6 and RAG-deficient mice, induced fatal disease. These data reveal unique structural features of IOE that may contribute to the pathogen's high virulence. ..
  29. Schmid C, Stienekemeier M, Oehen S, Bootz F, Zielasek J, Gold R, et al. Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance. J Neurosci. 2000;20:729-35 pubmed
    ..We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy. ..
  30. Bufalino A, Mayden R. Molecular phylogenetics of North American phoxinins (Actinopterygii: Cypriniformes: Leuciscidae) based on RAG1 and S7 nuclear DNA sequence data. Mol Phylogenet Evol. 2010;55:274-83 pubmed publisher
    ..Most analyses recovered a strongly supported shiner clade though, similar to several mtDNA studies; there was a high degree of topological variability among the results. ..
  31. Haq I, Steinberg L, Hoenig M, van der Burg M, Villa A, Cant A, et al. GvHD-associated cytokine polymorphisms do not associate with Omenn syndrome rather than T-B- SCID in patients with defects in RAG genes. Clin Immunol. 2007;124:165-9 pubmed
    ..No significant differences in allele frequencies were found between the groups, and no trends identified. The mechanisms determining the OS or T-B-NK+ SCID phenotype remain to be determined. ..
  32. Evans B, Kelley D, Melnick D, Cannatella D. Evolution of RAG-1 in polyploid clawed frogs. Mol Biol Evol. 2005;22:1193-207 pubmed
    ..Because of this, gene ancestry could potentially influence gene fate: interacting paralogs derived from the same lower ploidy ancestor might have similar genetic destinies. ..
  33. San Mauro D, Vences M, Alcobendas M, Zardoya R, Meyer A. Initial diversification of living amphibians predated the breakup of Pangaea. Am Nat. 2005;165:590-9 pubmed
  34. Taylor M, Hellberg M. Marine radiations at small geographic scales: speciation in neotropical reef gobies (Elacatinus). Evolution. 2005;59:374-85 pubmed
    ..Overall, speciation in Elacatinus is consistent with a model of recurring adaptive radiations in stages taking place at small geographic scales. ..
  35. Schatz D, Chun J. V(D)J recombination and the transgenic brain blues. New Biol. 1992;4:188-96 pubmed
  36. Zuccon D, Cibois A, Pasquet E, Ericson P. Nuclear and mitochondrial sequence data reveal the major lineages of starlings, mynas and related taxa. Mol Phylogenet Evol. 2006;41:333-44 pubmed
    ..The congruence between the age of major clades, estimated by NPRS, and palaeoclimatic data present evidence for the role of climatic changes in shaping present day distribution of the group...
  37. Lemaire M, Wésolowski Louvel M. Enolase and glycolytic flux play a role in the regulation of the glucose permease gene RAG1 of Kluyveromyces lactis. Genetics. 2004;168:723-31 pubmed
    ..Therefore, it seems that the enolase and a functional glycolytic flux are necessary for induction of expression of the Rag1 glucose permease in K. lactis. ..
  38. Buckley R. Advances in the understanding and treatment of human severe combined immunodeficiency. Immunol Res. 2000;22:237-51 pubmed
    ..5 mo of life, making early diagnosis crucial. Recently, gene therapy has also been successful in infants with X-linked SCID. ..
  39. Baker A, Pereira S, Haddrath O, Edge K. Multiple gene evidence for expansion of extant penguins out of Antarctica due to global cooling. Proc Biol Sci. 2006;273:11-7 pubmed
    ..Thus, global cooling has had a major impact on penguin evolution, as it has on vertebrates generally. Penguins only reached cooler tropical waters in the Galapagos about 4 mya, and have not crossed the equatorial thermal barrier. ..
  40. Durum S, Candeias S, Nakajima H, Leonard W, Baird A, Berg L, et al. Interleukin 7 receptor control of T cell receptor gamma gene rearrangement: role of receptor-associated chains and locus accessibility. J Exp Med. 1998;188:2233-41 pubmed
    ..This data supports the model that IL-7R promotes TCR-gamma gene rearrangement by regulating accessibility of the locus via demethylation and histone acetylation of the locus. ..
  41. Ericson P, Envall I, Irestedt M, Norman J. Inter-familial relationships of the shorebirds (Aves: Charadriiformes) based on nuclear DNA sequence data. BMC Evol Biol. 2003;3:16 pubmed
    ..The presented phylogenetic hypothesis provides a solid framework for analyses of macroevolution of ecological, morphological and behavioural adaptations observed within the order Charadriiformes. ..
  42. Diefenbach A, Hsia J, Hsiung M, Raulet D. A novel ligand for the NKG2D receptor activates NK cells and macrophages and induces tumor immunity. Eur J Immunol. 2003;33:381-91 pubmed
    ..Tumor cells ectopically expressing the molecule were efficiently rejected by naive mice, and induced strong protective immunity to the parental, ligand-negative tumor cells. ..
  43. Brandt V, Roth D. A recombinase diversified: new functions of the RAG proteins. Curr Opin Immunol. 2002;14:224-9 pubmed
  44. Peterson D, McNulty N, Guruge J, Gordon J. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe. 2007;2:328-39 pubmed
    ..Immunoselection of bacterial epitope expression may contribute to the remarkable strain-level diversity in this ecosystem. ..
  45. Su D, Manley N. Stage-specific changes in fetal thymocyte proliferation during the CD4-8- to CD4+8+ transition in wild type, Rag1-/-, and Hoxa3,Pax1 mutant mice. BMC Immunol. 2002;3:12 pubmed
    ..We also observed a decrease in the level of the cytokines IL-7 and SCF produced by Hoxa3+/-Pax1-/-TECs. Our results indicate complex and stage-specific effects of abnormal TEC development on thymocyte proliferation. ..
  46. Villa A, Sobacchi C, Notarangelo L, Bozzi F, Abinun M, Abrahamsen T, et al. V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations. Blood. 2001;97:81-8 pubmed
  47. Villa A, Sobacchi C, Vezzoni P. Recombination activating gene and its defects. Curr Opin Allergy Clin Immunol. 2001;1:491-5 pubmed
  48. Taylor M, Hellberg M. Comparative phylogeography in a genus of coral reef fishes: biogeographic and genetic concordance in the Caribbean. Mol Ecol. 2006;15:695-707 pubmed
    ..Our results, coupled with genetic and demographic data from other reef fishes and corals, provide robust support for the Mona Passage as a long-term biogeographic barrier for Caribbean animals. ..
  49. Carpenter A, Bassing C. Fetal thymocyte development: putting a zinc finger on it?. Nat Immunol. 2006;7:1285-6 pubmed
  50. Hu H, Wang B, Borde M, Nardone J, Maika S, Allred L, et al. Foxp1 is an essential transcriptional regulator of B cell development. Nat Immunol. 2006;7:819-26 pubmed
    ..Our results identify Foxp1 as an essential participant in the transcriptional regulatory network of B lymphopoiesis. ..
  51. Berghoff M, Samsam M, Müller M, Kobsar I, Toyka K, Kiefer R, et al. Neuroprotective effect of the immune system in a mouse model of severe dysmyelinating hereditary neuropathy: enhanced axonal degeneration following disruption of the RAG-1 gene. Mol Cell Neurosci. 2005;28:118-27 pubmed
    ..These data suggest a neuroprotective net effect of T-lymphocytes on axon survival in inherited, early onset dysmyelination. ..
  52. Muljo S, Schlissel M. The variable, C(H)1, C(H)2 and C(H)3 domains of Ig heavy chain are dispensable for pre-BCR function in transgenic mice. Int Immunol. 2002;14:577-84 pubmed
    ..These findings lead us to suggest that the majority of the extracellular region of the pre-BCR is not required for pre-BCR function and, thus, ligand binding is unlikely to be required for pre-BCR function. ..
  53. Fort M, Leach M, Rennick D. A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis. J Immunol. 1998;161:3256-61 pubmed
    ..Thus NK cells can play an important role in down-regulating Thl-mediated colitis by controlling the responses of effector T cells to gut bacteria. ..