vdj recombinases

Summary

Summary: Recombinases involved in the rearrangement of immunity-related GENES such as IMMUNOGLOBULIN GENES and T-CELL RECEPTOR GENES.

Top Publications

  1. ncbi RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination
    M A Oettinger
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
    Science 248:1517-23. 1990
  2. pmc RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons
    Vladimir V Kapitonov
    Genetic Information Research Institute, Mountain View, California, USA
    PLoS Biol 3:e181. 2005
  3. ncbi DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes
    U Grawunder
    University of Southern California School of Medicine, Norris Comprehensive Cancer Center, Department of Pathology, Los Angeles 90033, USA
    Mol Cell 2:477-84. 1998
  4. ncbi Unraveling V(D)J recombination; insights into gene regulation
    David Jung
    Howard Hughes Medical Institute, The Children s Hospital, The CBR Institute for Biomedical Research, Inc, Harvard Medical School, Boston, MA 02115, USA
    Cell 116:299-311. 2004
  5. ncbi RAG1-DNA binding in V(D)J recombination. Specificity and DNA-induced conformational changes revealed by fluorescence and CD spectroscopy
    Mihai Ciubotaru
    Howard Hughes Medical Institute, Yale University School of Medicine, Section of Immunobiology, New Haven, Connecticut 06510, USA
    J Biol Chem 278:5584-96. 2003
  6. ncbi The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development
    Hong Erh Liang
    Department of Molecular and Cell Biology, Division of Immunology, University of California, Berkeley 94720, USA
    Immunity 17:639-51. 2002
  7. pmc B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors
    Lisa Borghesi
    Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester 01655, USA
    J Exp Med 199:491-502. 2004
  8. ncbi Mechanisms of chromosomal translocations in B cell lymphomas
    R Kuppers
    Institute of Cancer Genetics, Columbia University, New York, NY 10032, USA
    Oncogene 20:5580-94. 2001
  9. ncbi Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor
    A E Corcoran
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nature 391:904-7. 1998
  10. pmc A non-sequence-specific DNA binding mode of RAG1 is inhibited by RAG2
    Shuying Zhao
    Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA
    J Mol Biol 387:744-58. 2009

Detail Information

Publications172 found, 100 shown here

  1. ncbi RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination
    M A Oettinger
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142
    Science 248:1517-23. 1990
    ..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...
  2. pmc RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons
    Vladimir V Kapitonov
    Genetic Information Research Institute, Mountain View, California, USA
    PLoS Biol 3:e181. 2005
    ..We also suggest that the RAG2 protein was not encoded by ancient Transib transposons but emerged in jawed vertebrates as a counterpart of RAG1 necessary for the V(D)J recombination reaction...
  3. ncbi DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes
    U Grawunder
    University of Southern California School of Medicine, Norris Comprehensive Cancer Center, Department of Pathology, Los Angeles 90033, USA
    Mol Cell 2:477-84. 1998
    ..Hence, DNA ligase IV is the activity responsible for the ligation step in NHEJ and in V(D)J recombination...
  4. ncbi Unraveling V(D)J recombination; insights into gene regulation
    David Jung
    Howard Hughes Medical Institute, The Children s Hospital, The CBR Institute for Biomedical Research, Inc, Harvard Medical School, Boston, MA 02115, USA
    Cell 116:299-311. 2004
    ....
  5. ncbi RAG1-DNA binding in V(D)J recombination. Specificity and DNA-induced conformational changes revealed by fluorescence and CD spectroscopy
    Mihai Ciubotaru
    Howard Hughes Medical Institute, Yale University School of Medicine, Section of Immunobiology, New Haven, Connecticut 06510, USA
    J Biol Chem 278:5584-96. 2003
    ..RSS-induced conformational changes of StrRAG1 may influence the interaction of RAG1 with RAG2 and synaptic complex formation...
  6. ncbi The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development
    Hong Erh Liang
    Department of Molecular and Cell Biology, Division of Immunology, University of California, Berkeley 94720, USA
    Immunity 17:639-51. 2002
    ....
  7. pmc B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors
    Lisa Borghesi
    Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester 01655, USA
    J Exp Med 199:491-502. 2004
    ..As activity of the Erag enhancer is restricted to the B cell lineage, this provides the first molecular evidence for establishment of a lineage-specific transcription program in multipotent progenitors...
  8. ncbi Mechanisms of chromosomal translocations in B cell lymphomas
    R Kuppers
    Institute of Cancer Genetics, Columbia University, New York, NY 10032, USA
    Oncogene 20:5580-94. 2001
    ....
  9. ncbi Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor
    A E Corcoran
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nature 391:904-7. 1998
    ..This mechanism augments the recombinational diversity of the primary antibody repertoire...
  10. pmc A non-sequence-specific DNA binding mode of RAG1 is inhibited by RAG2
    Shuying Zhao
    Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA
    J Mol Biol 387:744-58. 2009
    ....
  11. pmc Developmental separation of V(D)J recombinase expression and initiation of IgH recombination in B lineage progenitors in vivo
    Lisa Borghesi
    University of Massachusetts Medical School, Molecular Genetics and Microbiology, 55 Lake Ave North, Worcester 01655, USA
    J Exp Med 199:483-9. 2004
    ..Our results indicate that the onset of recombinase activity and the initiation of IgH recombination are developmentally distinct events in the B lineage...
  12. ncbi B cell progenitors are arrested in maturation but have intact VDJ recombination in the absence of Ig-alpha and Ig-beta
    Roberta Pelanda
    Biologie III, University of Freiburg and Max Planck Institute for Immunobiology, Freiburg, Germany
    J Immunol 169:865-72. 2002
    ..Finally, Ig-alpha and Ig-beta are not redundant in their putative function, as pro-B cells from Ig-alpha and Ig-beta double-deficient mice are similar to those from single-deficient animals in every aspect analyzed...
  13. pmc Commitment to the B lymphoid lineage occurs before DH-JH recombination
    D Allman
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Exp Med 189:735-40. 1999
    ....
  14. pmc Enhancer control of V(D)J recombination at the TCRbeta locus: differential effects on DNA cleavage and joining
    W M Hempel
    Centre d Immunologie Institut National de la Santé et de la Recherche Médicale Centre National de la Recherche Scientifique de Marseille Luminy, Marseille Cedex 9, France
    Genes Dev 12:2305-17. 1998
    ....
  15. pmc Accessibility of chromosomal recombination breaks in nuclei of wild-type and DNA-PKcs-deficient cells
    Daniel Franco
    Molecular and Cellular Biology Program, School of Life Sciences, Center for Infectious Diseases and Vaccinology, The Biodesign Institute at Arizona State University, BDA220, 1001 S McAllister Avenue, Tempe, AZ 85287 5501, United States
    DNA Repair (Amst) 8:813-21. 2009
    ..e., the greater the accessibility of the coding ends, the higher level of coding joints formed. Taken together, our findings provide important insights into the resolution of recombination ends by error-prone alternative NHEJ pathways...
  16. ncbi Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes
    T Komori
    Howard Hughes Medical Institute, Children s Hospital, Boston, MA 02115
    Science 261:1171-5. 1993
    ....
  17. pmc Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros
    Damien Reynaud
    Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA
    Nat Immunol 9:927-36. 2008
    ..Thus, Ikaros is an obligate component of a network that regulates B cell fate commitment and immunoglobulin heavy-chain gene recombination...
  18. ncbi The mechanism of vertebrate nonhomologous DNA end joining and its role in V(D)J recombination
    Michael R Lieber
    USC Norris Comprehensive Cancer Ctr, Rm 5428, University of Southern California Keck School of Medicine, Department of Pathology, Los Angeles, CA 90033, USA
    DNA Repair (Amst) 3:817-26. 2004
    ..The NHEJ pathway is needed to repair these physiologic breaks, as well as challenging pathologic breaks that arise from ionizing radiation and oxidative damage to DNA...
  19. ncbi Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B-severe combined immune deficiency or Omenn syndrome
    B Corneo
    Developpement Normal et Pathologique du Systeme Immunitaire, Hopital Necker Enfants Malades, Paris, France
    Blood 97:2772-6. 2001
    ..The nature of this factor is discussed...
  20. ncbi Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complex
    S D Fugmann
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Mol Cell 5:97-107. 2000
    ....
  21. ncbi The V(D)J recombinase efficiently cleaves and transposes signal joints
    Matthew B Neiditch
    Department of Immunology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Cell 9:871-8. 2002
    ....
  22. pmc Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice
    Darryll D Dudley
    Howard Hughes Medical Institute, The Children s Hospital, The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 198:1439-50. 2003
    ..We discuss the potential implications of these findings for noncore RAG1 functions and for the ordered assembly of VH, DH, and JH segments...
  23. ncbi The V(D)J recombination activating gene, RAG-1
    D G Schatz
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142
    Cell 59:1035-48. 1989
    ..RAG-1 may activate V(D)J recombination indirectly, or it may encode the V(D)J recombinase itself...
  24. pmc N-terminal RAG1 frameshift mutations in Omenn's syndrome: internal methionine usage leads to partial V(D)J recombination activity and reveals a fundamental role in vivo for the N-terminal domains
    S Santagata
    Ruttenberg Cancer Center, Immunobiology Center, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA
    Proc Natl Acad Sci U S A 97:14572-7. 2000
    ..Taken together, our results suggest a novel mechanism for the development of immunodeficiency in a subset of Omenn's syndrome patients...
  25. ncbi Recombination signal sequence variations and the mechanism of patterned T-cell receptor-beta locus rearrangement
    Alexandru Olaru
    Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore, 655 West Baltimore Street, BRB 13 017, Baltimore, MD 21201, USA
    Mol Immunol 40:1189-201. 2004
    ....
  26. pmc Sensing of intermediates in V(D)J recombination by ATM
    Eric J Perkins
    Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Genes Dev 16:159-64. 2002
    ..We suggest routine surveillance of intermediates in V(D)J recombination by ATM helps suppress potentially oncogenic translocations when repair fails...
  27. ncbi RAG proteins shepherd double-strand breaks to a specific pathway, suppressing error-prone repair, but RAG nicking initiates homologous recombination
    Gregory S Lee
    The Skirball Institute of Biomolecular Medicine, Lab 2 10 and Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
    Cell 117:171-84. 2004
    ..We also find that RAG-mediated nicks efficiently stimulate homologous recombination and discuss the implications of these findings for oncogenic chromosomal rearrangements, evolution, and gene targeting...
  28. ncbi Single-strand recombination signal sequence nicks in vivo: evidence for a capture model of synapsis
    John D Curry
    Department of Molecular and Cell Biology, Division of Immunology, University of California, Berkeley, California 94720 3200, USA
    Nat Immunol 6:1272-9. 2005
    ..These data support a model of capture rather than synapsis for pairwise RSS cleavage during V(D)J recombination...
  29. pmc Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene
    Martin Fuxa
    Research Institute of Molecular Pathology, Vienna Biocente, A 1030 Vienna, Austria
    Genes Dev 18:411-22. 2004
    ..Pax5 subsequently activates locus contraction and distal VH-DJH rearrangements in collaboration with an unknown factor that is present in pro-B cells, but absent in thymocytes...
  30. ncbi Separation-of-function mutants reveal critical roles for RAG2 in both the cleavage and joining steps of V(D)J recombination
    J X Qiu
    Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA
    Mol Cell 7:77-87. 2001
    ..Moreover, the discovery that some mutants block RAG-mediated hairpin opening in vitro provides a critical link between this biochemical activity and coding joint formation in vivo...
  31. pmc Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments
    David G T Hesslein
    Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520 8011, USA
    Genes Dev 17:37-42. 2003
    ..The finding of transcribed, histone acetylated gene segments that fail to recombine suggests that a Pax5-dependent regulatory mechanism is required in addition to standard constraints of accessibility to control V(H) gene recombination...
  32. pmc Pax5 activates immunoglobulin heavy chain V to DJ rearrangement in transgenic thymocytes
    Lih Yun Hsu
    Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, 94720, USA
    J Exp Med 199:825-30. 2004
    ....
  33. ncbi A PHD finger motif in the C terminus of RAG2 modulates recombination activity
    Sheryl K Elkin
    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Biol Chem 280:28701-10. 2005
    ..We propose a model in which the equilibrium between these states modulates recombination activity. Together, these data identify the PHD finger as a novel and functionally important domain of RAG2...
  34. pmc Intermediates in V(D)J recombination: a stable RAG1/2 complex sequesters cleaved RSS ends
    J M Jones
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 241, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 98:12926-31. 2001
    ..Sequestration of cleaved ends within the signal end complex would account for the persistence of these ends in the cell after cleavage and may explain why they do not normally activate the DNA-damage-dependent cell cycle checkpoint...
  35. ncbi Identification of anti-herpes simplex virus antibody-producing B cells in a patient with an atypical RAG1 immunodeficiency
    S Kumaki
    Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
    Blood 98:1464-8. 2001
    ....
  36. pmc Localized gene-specific induction of accessibility to V(D)J recombination induced by E2A and early B cell factor in nonlymphoid cells
    P Goebel
    The Scripps Research Institute, Department of Immunology IMM-22, La Jolla, CA 92037, USA
    J Exp Med 194:645-56. 2001
    ..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...
  37. ncbi V(D)J recombination and RAG-mediated transposition in yeast
    Anne E Clatworthy
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Mol Cell 12:489-99. 2003
    ..Cleaved signal ends are also transposed into new sites in DNA, allowing RAG-induced transposition to be studied in vivo...
  38. pmc Overlapping signals for protein degradation and nuclear localization define a role for intrinsic RAG-2 nuclear uptake in dividing cells
    Ashley E Ross
    Department of Molecular Biology and Genetics and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA
    Mol Cell Biol 23:5308-19. 2003
    ..These results suggest that the intrinsic RAG-2 NLS functions in the nuclear uptake of RAG-2 following its reexpression in cycling cells...
  39. ncbi 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
    C A Roman
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Immunity 7:13-24. 1997
    ..Our data suggest that the RAG-1 N-terminus enhances the formation of an active recombination complex that facilitates the rearrangement process...
  40. ncbi Access roads for RAG-ged terrains: control of T cell receptor gene rearrangement at multiple levels
    Ferenc Livak
    Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA
    Semin Immunol 14:297-309. 2002
    ..The emerging results suggest that formation of the primary repertoire is controlled by two, partially independent factors: chromosomal accessibility and direct recombinase-DNA interactions...
  41. pmc Functions of E2A-HEB heterodimers in T-cell development revealed by a dominant negative mutation of HEB
    R J Barndt
    Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 20:6677-85. 2000
    ..These results indicate that E2A-HEB heterodimers play obligatory roles both before and after TCRbeta gene rearrangement during the alpha/beta lineage T-cell development...
  42. pmc Roles for NBS1 in alternative nonhomologous end-joining of V(D)J recombination intermediates
    Ludovic Deriano
    Department of Pathology, The Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine and, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 34:13-25. 2009
    ..These data demonstrate that the MRE11 complex functions at two distinct levels, regulating repair pathway choice (likely through enhancing the stability of DNA end complexes) and participating in alternative NHEJ of coding ends...
  43. pmc RAG: a recombinase diversified
    Adam G W Matthews
    Howard Hughes Medical Institute, Department of Biology, Cambridge, Massachusetts, USA
    Nat Immunol 10:817-21. 2009
    ..Here we discuss some of these functions and suggest that the RAG-1-RAG-2 complex nucleates a specialized subnuclear compartment that we call the 'V(D)J recombination factory'...
  44. ncbi Cutting edge: targeting of V beta to D beta rearrangement by RSSs can be mediated by the V(D)J recombinase in the absence of additional lymphoid-specific factors
    Robert E Tillman
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110 1093, USA
    J Immunol 170:5-9. 2003
    ..These findings demonstrate that targeting of Vbeta to Dbeta rearrangement can be enforced by the V(D)J recombinase in the absence of lymphoid-specific factors other than the recombinase-activating gene-1/2 proteins...
  45. ncbi Restraining the V(D)J recombinase
    David B Roth
    Department of Pathology, Program in Molecular Pathogenesis, Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York 10016, USA
    Nat Rev Immunol 3:656-66. 2003
    ..What mechanisms constrain the dangerous potential of the recombinase and preserve genomic integrity during immune-system development?..
  46. ncbi DNA-Rag protein interactions in the control of selective D gene utilization in the TCR beta locus
    Alexandru Olaru
    Department of Microbiology and Immunology, Graduate Program in Molecular and Cellular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    J Immunol 171:3605-11. 2003
    ....
  47. pmc Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4
    Katrina B Morshead
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 100:11577-82. 2003
    ..The specific patterns of modification imply that the regulation of V(D)J recombination involves recruitment of specific methyltransferases in a localized manner...
  48. pmc Ordered assembly of the V(D)J synaptic complex ensures accurate recombination
    Jessica M Jones
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5 Room 241, Bethesda, MD 20892, USA
    EMBO J 21:4162-71. 2002
    ..Additional cellular factors such as chromatin may ensure that RAG1/2 first assembles on a 12 RSS, and then a free 23 RSS enters to activate cleavage...
  49. pmc In vivo transposition mediated by V(D)J recombinase in human T lymphocytes
    Terri L Messier
    Department of Pediatrics, University of Vermont, Burlington, VT 05405, USA
    EMBO J 22:1381-8. 2003
    ..These findings implicate V(D)J recombinase-mediated transposition as a mutagenic mechanism capable of deleterious genetic rearrangements in humans...
  50. pmc Targeted transposition by the V(D)J recombinase
    Gregory S Lee
    Department of Immunology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 22:2068-77. 2002
    ..The RAG proteins are capable of mediating all necessary breakage and joining events on both partner chromosomes; thus, the V(D)J recombinase may be far more culpable for oncogenic translocations than has been suspected...
  51. pmc A functional analysis of the spacer of V(D)J recombination signal sequences
    Alfred Ian Lee
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
    PLoS Biol 1:E1. 2003
    ..quot; The interplay between such binary and multiplicative modes of interactions provides a general model for analyzing protein-DNA interactions in various biological systems...
  52. pmc Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice
    Yoshiko Akamatsu
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 100:1209-14. 2003
    ..We discuss potential roles of the RAG2 C terminus in mediating rearrangement of endogenous antigen-receptor loci...
  53. ncbi Leaky Scid phenotype associated with defective V(D)J coding end processing in Artemis-deficient mice
    Sean Rooney
    Howard Hughes Medical Institute, The Children s Hospital, The Center for Blood Research, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
    Mol Cell 10:1379-90. 2002
    ..Finally, Artemis deficiency leads to chromosomal instability in fibroblasts, demonstrating that Artemis functions as a genomic caretaker...
  54. pmc Understanding how the V(D)J recombinase catalyzes transesterification: distinctions between DNA cleavage and transposition
    Catherine P Lu
    Program in Molecular Pathogenesis, Department of Pathology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Nucleic Acids Res 36:2864-73. 2008
    ..These findings provide the first identification of components of Rag1 that are specifically required for transesterification and suggest an unexpected role for Rag2 in DNA cleavage and transposition...
  55. ncbi Full-length RAG-2, and not full-length RAG-1, specifically suppresses RAG-mediated transposition but not hybrid joint formation or disintegration
    Patrick C Swanson
    Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, Nebraska 68178, USA
    J Biol Chem 279:4034-44. 2004
    ....
  56. ncbi The mechanism and regulation of chromosomal V(D)J recombination
    Craig H Bassing
    Howard Hughes Medical Institute, The Children s Hospital, The Center for Blood Research, Boston, MA 02115, USA
    Cell 109:S45-55. 2002
    ..We review our current understanding of the V(D)J recombination reaction and how it is regulated during lymphocyte development. We also discuss how defects in the mechanism or regulation of V(D)J recombination can lead to human disease...
  57. pmc Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination
    Chia Lun Tsai
    Department of Molecular Biophysics and Biochemistry, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Genes Dev 16:1934-49. 2002
    ..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...
  58. pmc Mutational analysis of all conserved basic amino acids in RAG-1 reveals catalytic, step arrest, and joining-deficient mutants in the V(D)J recombinase
    Leslie E Huye
    Department of Immunolog, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 22:3460-73. 2002
    ..Our analysis of these mutants provides insights into the molecular mechanisms underlying these disorders...
  59. ncbi V(D)J recombination
    David G Schatz
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 8011, USA
    Immunol Rev 200:5-11. 2004
  60. ncbi The phylogenetic origins of the antigen-binding receptors and somatic diversification mechanisms
    John P Cannon
    Department of Molecular Genetics, All Children s Hospital, St Petersburg, FL, USA
    Immunol Rev 200:12-22. 2004
    ..Such studies have the potential for uncovering previously unknown mechanisms of generating receptor diversity...
  61. pmc Genomic instability due to V(D)J recombination-associated transposition
    Yeturu V R Reddy
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Genes Dev 20:1575-82. 2006
    ..In total, transposition occurred approximately once every 50,000 V(D)J recombinations. Transposition may thus contribute significantly to genomic instability...
  62. ncbi V(D)J recombinase mediated inter-chromosomal HPRT alterations at cryptic recombination signal sequences in peripheral human T cells
    Terri L Messier
    Department of Pediatrics, University of Vermont, Burlington, Vermont, USA
    Hum Mutat 27:829. 2006
    ....
  63. ncbi Accessibility control of V(D)J recombination
    Robin Milley Cobb
    Department of Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, USA
    Adv Immunol 91:45-109. 2006
    ..The discussion will focus on cis-acting regulation by ACEs, the nuclear factors that control ACE function, and the epigenetic modifications that establish recombinase accessibility...
  64. ncbi Amino acid residues in Rag1 crucial for DNA hairpin formation
    Catherine P Lu
    Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, and Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
    Nat Struct Mol Biol 13:1010-5. 2006
    ..Other residues surrounding the catalytic glutamate (YKEFRK) may share functional similarities with the YREK motif in IS4 family transposases...
  65. ncbi Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus
    S L Nutt
    Research Institute of Molecular Pathology, Vienna, Austria
    Genes Dev 11:476-91. 1997
    ..In contrast, V(H)-to-D(H)J(H) rearrangements were reduced approximately 50-fold in Pax5-deficient pre-BI cells, suggesting a role for Pax5 in the developmental pathway controlling V-to-DJ recombination...
  66. pmc Assessing the pathogenic potential of the V(D)J recombinase by interlocus immunoglobulin light-chain gene rearrangement
    S N Bailey
    Department of Pathology and Graduate Program in Immunology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Mol Cell Biol 17:887-94. 1997
    ..Considering the large numbers of lymphocytes generated throughout life, aberrant rearrangements generated by the V(D)J recombinase may be relatively common...
  67. ncbi Neoteny in lymphocytes: Rag1 and Rag2 expression in germinal center B cells
    S Han
    Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA
    Science 274:2094-7. 1996
    ..Germinal center B cells thus share fundamental characteristics of immature lymphocytes, raising the possibility that antigen-dependent secondary V(D)J rearrangements modify the peripheral antibody repertoire...
  68. ncbi The DDE recombinases: diverse roles in acquired and innate immunity
    David H Dreyfus
    Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut 06511, USA
    Ann Allergy Asthma Immunol 97:567-76; quiz 576-8, 602. 2006
    ..A similar DDE-like magnesium binding site also is present in transposases, retroviral integrases, and the innate antiviral response enzymes RNAse H and RNA-induced silencing complex (RISC)...
  69. pmc DNA sequence and structure requirements for cleavage of V(D)J recombination signal sequences
    C A Cuomo
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 16:5683-90. 1996
    ..Sequence alterations that facilitate unpairing of the bases at the signal/coding border activate the cleavage reaction, suggesting that DNA distortion is critical for V(D)J recombination...
  70. pmc Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer: the role of enhancer elements in controlling V(D)J recombination accessibility
    J C Bories
    Unité 93, Institut National de la Sante et de la Recherche Medicale, Hopital Saint Louis, Paris, France
    Proc Natl Acad Sci U S A 93:7871-6. 1996
    ..These results demonstrate a critical role for Ebeta in promoting accessibility of the TCRbeta locus and suggest that additional negative elements may cooperate to further modulate this process...
  71. pmc RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination
    Adam G W Matthews
    Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 450:1106-10. 2007
    ..Furthermore, our results provide the first evidence indicating that disrupting the read-out of histone modifications can cause an inherited human disease...
  72. ncbi Regulation of Tcrb recombination ordering by c-Fos-dependent RAG deposition
    Xiaoming Wang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Nat Immunol 9:794-801. 2008
    ..Our results show an unexpected function for c-Fos as a direct regulator of Tcrb recombination, rather than its usual function as a transcription regulator, and provide new insight into the mechanisms of recombination ordering...
  73. ncbi Formation and resolution of double-strand break intermediates in V(D)J rearrangement
    D A Ramsden
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0540, USA
    Genes Dev 9:2409-20. 1995
    ..Efficient formation of signal junctions may require cell cycle progression, or down-regulation of the recombination machinery...
  74. ncbi DNA cleavage of a cryptic recombination signal sequence by RAG1 and RAG2. Implications for partial V(H) gene replacement
    Negar S Rahman
    Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA
    J Biol Chem 281:12370-80. 2006
    ..These results have implications for further diversification of the antigen receptor repertoire as well as the role of the RAG proteins in genomic instability...
  75. ncbi The bounty of RAGs: recombination signal complexes and reaction outcomes
    Patrick C Swanson
    Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, NE 68178, USA
    Immunol Rev 200:90-114. 2004
    ..Finally, I discuss alternative DNA transactions mediated by the V(D)J recombinase, the protein-DNA complexes that support them, and factors and forces that control them...
  76. ncbi The taming of a transposon: V(D)J recombination and the immune system
    Jessica M Jones
    Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington DC, USA
    Immunol Rev 200:233-48. 2004
    ..This work highlights the considerable diversity of transposition systems and their relation to V(D)J recombination...
  77. ncbi Analysis of the V(D)J recombination efficiency at lymphoid chromosomal translocation breakpoints
    S C Raghavan
    Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90089 9176, USA
    J Biol Chem 276:29126-33. 2001
    ..These results quantify one of the three major factors that determine the frequency of these translocations in T-cell acute lymphocytic leukemia...
  78. ncbi Regulation of T-cell receptor beta-chain gene assembly by recombination signals: the beyond 12/23 restriction
    Robert E Tillman
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110 1093, USA
    Immunol Rev 200:36-43. 2004
    ..By preserving Dbeta gene segment utilization, the B12/23 restriction is required, at a minimum, for the generation of a diverse repertoire of TCRbeta chains...
  79. ncbi New concepts in the regulation of an ancient reaction: transposition by RAG1/RAG2
    Monalisa Chatterji
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Immunol Rev 200:261-71. 2004
    ..A major challenge has been to determine how the transposition activity of the RAG proteins is regulated in vivo. Although a variety of mechanisms have been suggested by recent studies, a clear resolution of this issue remains elusive...
  80. ncbi Joining mutants of RAG1 and RAG2 that demonstrate impaired interactions with the coding-end DNA
    Fumikiyo Nagawa
    Department of Biophysics and Biochemistry, Graduate School of Science, and Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency, The University of Tokyo, Bunkyo ku, Tokyo 113 0032, Japan
    J Biol Chem 279:38360-8. 2004
    ..A possible role of this RAG coding region interaction is discussed in the context of V(D)J recombination...
  81. pmc DNA cleavage activity of the V(D)J recombination protein RAG1 is autoregulated
    Pallabi De
    Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA
    Mol Cell Biol 24:6850-60. 2004
    ..We propose how the combined actions of the RAG1 domains may function in V(D)J recombination and also in aberrant cleavage reactions that may lead to genomic instability in B and T lymphocytes...
  82. ncbi Deletion of germline promoter PD beta 1 from the TCR beta locus causes hypermethylation that impairs D beta 1 recombination by multiple mechanisms
    C E Whitehurst
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Immunity 13:703-14. 2000
    ..These findings suggest that methylation can regulate V(D)J recombination both at a general level by influencing regional chromatin accessibility and specifically by blocking RSS recognition or cleavage by the V(D)J recombinase...
  83. ncbi A direct interaction between the RAG2 C terminus and the core histones is required for efficient V(D)J recombination
    Kelly L West
    Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA
    Immunity 23:203-12. 2005
    ..Point mutations that disrupt the RAG2-histone association inhibit the efficiency of the V(D)J recombination reaction at the endogenous immunoglobulin locus, with the most dramatic effect in the V to DJ(H) rearrangement...
  84. pmc Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase
    D R Kim
    Molecular Biology Department, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Genes Dev 13:3070-80. 1999
    ..Our results support a model in which the RAG1 protein contains the active site of the V(D)J recombinase and are interpreted in light of predictions about the structure of RAG1...
  85. pmc Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination
    M A Landree
    Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 13:3059-69. 1999
    ..These data suggest that RAG-mediated DNA cleavage involves coordination of divalent metal ion(s) by RAG1...
  86. ncbi Turning T-cell receptor beta recombination on and off: more questions than answers
    Annette M Jackson
    Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA
    Immunol Rev 209:129-41. 2006
    ..We highlight the many unresolved issues and we discuss how recent concepts emerging from studies of other antigen receptor loci may (or may not) help to resolve these issues...
  87. pmc Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair
    Qi Ding
    College of Veterinary Medicine and Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan 48824, USA
    Mol Cell Biol 23:5836-48. 2003
    ..However, autophosphorylation at these sites may not be sufficient for kinase disassembly...
  88. pmc Alternative pathways for the repair of RAG-induced DNA breaks
    David M Weinstock
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Mol Cell Biol 26:131-9. 2006
    ..Thus, RAG-generated DSBs are typically repaired by the NHEJ pathway in ES cells, but in the absence of NHEJ components, a substantial fraction of breaks can be efficiently channeled into alternative pathways in these cells...
  89. ncbi Biochemistry of V(D)J recombination
    D G Schatz
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520 8011, USA
    Curr Top Microbiol Immunol 290:49-85. 2005
    ..We discuss how the RAG proteins interact with DNA and how coordinate cleavage of the DNA at two sites might be achieved. Finally, we consider the RAG proteins and V(D)J recombination from an evolutionary point of view...
  90. ncbi The ontogeny and fate of NK cells marked by permanent DNA rearrangements
    Kristy Pilbeam
    Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA
    J Immunol 180:1432-41. 2008
    ....
  91. ncbi Induction of V(D)J-mediated recombination of an extrachromosomal substrate following exposure to DNA-damaging agents
    Robert L Pinsonneault
    Department of Pediatrics, University of Vermont, Burlington, Vermont, USA
    Environ Mol Mutagen 48:440-50. 2007
    ....
  92. ncbi V(D)J recombination: how to tame a transposase
    Vicky L Brandt
    Program in Molecular Pathogenesis, The Skirball Institute, New York University School of Medicine, New York, NY, USA
    Immunol Rev 200:249-60. 2004
    ..These novel strategies for harnessing the RAG transposase not only shed light on V(D)J recombination but also may provide insight into the regulation of other transposases...
  93. pmc V(D)J recombination and the evolution of the adaptive immune system
    Eleonora Market
    Rockefeller University, New York, New York, USA
    PLoS Biol 1:E16. 2003
  94. pmc Quantitative analyses of RAG-RSS interactions and conformations revealed by atomic force microscopy
    Jeffrey W Pavlicek
    School of Life Sciences, Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, Arizona 85287 5501, USA
    Biochemistry 47:11204-11. 2008
    ....
  95. ncbi Does artemis end the hunt for the hairpin-opening activity in V(D)J recombination?
    Mark S Schlissel
    Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Cell 109:1-4. 2002
    ..Both genetic and biochemical data point toward a physiological role for this complex as the elusive hairpin-opening activity in V(D)J recombination...
  96. ncbi V(D)J recombination is not required for the development of lymphoma in p53-deficient mice
    M Nacht
    Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA
    Cell Growth Differ 9:131-8. 1998
    ..These data suggest that normal V(D)J recombination is not required for the development of thymic lymphoma in the context of a p53 germ-line mutation...
  97. ncbi RAG-1 and RAG-2 gene expression and V(D)J recombinase activity are enhanced by protein phosphatase 1 and 2A inhibition in lymphocyte cell lines
    A M Casillas
    Department of Biology, University of California at Los Angeles 90024
    Mol Immunol 32:167-75. 1995
    ..These results suggest novel intracellular mechanisms for the upregulation of RAG gene expression and confirm a role for type 1 and 2A phosphatases in the control of RAG gene expression and recombinase activity in lymphocyte cell lines...
  98. ncbi Control of chromatin accessibility for V(D)J recombination by interleukin-7
    J Huang
    Laboratory of Molecular Immuneregulation, SAIC-FCRDC, National Cancer Institute, Frederick, Maryland, USA
    J Leukoc Biol 69:907-11. 2001
    ..This opening leads to a higher accessibility for the transcription machinery and increased accessibility of the Rag heterodimer that performs the cleavage of DNA...
  99. pmc Functional organization of single and paired V(D)J cleavage complexes
    M A Landree
    Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 21:4256-64. 2001
    ..These results strongly suggest that two RAG-1 dimers are responsible for RSS cleavage in a synaptic complex, with one monomer of each dimer catalyzing both nicking and hairpin formation at each RSS...
  100. ncbi DNA repair: spot(light)s on chromatin
    M Modesti
    Department of Cell Biology and Genetics, Erasmus University Rotterdam, PO Box 1738, 3000 DR, Rotterdam, The Netherlands
    Curr Biol 11:R229-32. 2001
    ..Recent studies on the phosphorylation of a histone 2A variant have revealed that this chromatin modification is a general and evolutionarily conserved cellular response to DNA double-strand breaks...
  101. pmc The RAG proteins in V(D)J recombination: more than just a nuclease
    M J Sadofsky
    Medical College of Georgia, Institute of Molecular Medicine and Genetics, CB 2803, Augusta, GA 30912, USA
    Nucleic Acids Res 29:1399-409. 2001
    ..Two proteins, RAG1 and RAG2, together form the nuclease that cleaves the DNA at the border of the signal sequences. Additional roles of these proteins in organizing the reaction complex for subsequent steps are explored...

Research Grants57

  1. Regulation of the VDJ recombinase during genotoxic stress
    Karla K Rodgers; Fiscal Year: 2013
    ..The ability to enhance such a regulatory process may lead to decreased risks of developing lymphoid malignancies following exposure to radiation and other DNA damaging drugs. ..
  2. Long-Range Genetic and Epigenetic Control of Igh Gene Assembly
    Eugene M Oltz; Fiscal Year: 2010
    ..We propose studies to address how precursor B cells control long-range changes in the spatial organization of the immunoglobulin heavy chain locus to ensure its proper assembly and pursuant generation of an adaptive immune system. ..
  3. LOCALIZED REVISION OF EPIGENETIC LANDSCAPES INDUCED BY DNA DOUBLE-STRAND BREAKS
    Barry P Sleckman; Fiscal Year: 2012
    ..We now propose to identify histone modifications that function as intermediates to coordinate the normal repair of DNA-DSBs in mammalian cells. ..
  4. Accessibility Control of Antigen Receptor Gene Assembly
    Eugene M Oltz; Fiscal Year: 2013
    ..We propose studies to address how precursor T lymphocytes activate the T cell receptor beta locus at the earliest stages of thymocyte development to ensure its proper assembly by V(D)J recombination. ..
  5. Long-Range Genetic and Epigenetic Control of Tcrb Gene Assembly
    Eugene M Oltz; Fiscal Year: 2010
    ..We propose studies to address how precursor T lymphocytes control long-range changes in the spatial organization of T cell receptor beta loci to ensure their proper assembly and pursuant generation of a normal adaptive immune system. ..
  6. Spatiotemporal control of recombination by the RAG proteins and ATM
    JANE AMANDA SKOK; Fiscal Year: 2010
    ..We propose to further these studies to understand precisely how these factors achieve these unexpected effects. ..
  7. BIOCHEMISTRY AND REGULATION OF V(D)J RECOMBINATION
    Mark S Schlissel; Fiscal Year: 2012
    ..Our approach is to take what has been learned in vitro and use it to frame and test hypotheses regarding the regulation of recombination in vivo. ..
  8. NORMAL AND MUTANT LYMPHOID V(D)J RECOMBINASE
    Michael R Lieber; Fiscal Year: 2011
    ..In the long-term, all of these studies will help establish optimal therapy for many human SCID patients and to understand the human immune repertoire. ..
  9. Temporal and Spatial Control of V(D)J Recombination
    STEPHEN V DESIDERIO; Fiscal Year: 2013
    ....
  10. Optimal Generation and Characterization of iPS Cell Lines from Healthy and ADHD S
    Kwang Soo Kim; Fiscal Year: 2012
    ..This approach will advance the iPS cell technology and provide a platform for investigating the biological and molecular mechanisms underlying ADHD pathogenesis. ..
  11. Optimal Generation and Characterization of iPS Cell Lines from Healthy and ADHD S
    Kwang Soo Kim; Fiscal Year: 2010
    ..This approach will advance the iPS cell technology and provide a platform for investigating the biological and molecular mechanisms underlying ADHD pathogenesis. ..
  12. Molecular basis of the requirements for IRF4 and IRF8 in pre-B cell development
    Runqing Lu; Fiscal Year: 2010
    ..In the absence of IRF4,8, pro-B cell development appears to be normal but pre-B cell development is blocked. We hypothesize that expression of IRF4,8 is induced at the pre-B stage by pre-BCR though Blnk/Btk-mediated signaling. ..
  13. EXPRESSION OF IMMUNOGLOBULIN GENES IN TRANSGENIC MICE
    Ursula Storb; Fiscal Year: 2000
    ..It is expected that these experiments will contribute to the understanding of the control of B cell development and Ig gene expression, and will provide new insights into immunological disorders with a B cell component. ..
  14. CONTROL OF IMMUNOGLOBULIN SYNTHESIS
    Ursula Storb; Fiscal Year: 2001
    ..Understanding this mechanism will provide a fundamental basis for the unraveling of many diseases involving the immune system, such as autoimmunities, infectious diseases, allergies and cancer. ..
  15. SOMATIC DNA RECOMBINATION IN ANTIBODY GENES
    Hitoshi Sakano; Fiscal Year: 1993
    ..They will also shed light on the basic processes of some immunodeficiencies and chromosome abnormalities caused by DNA arrangement...
  16. MOLECULAR CONTROL OF ANTIGEN RECEPTOR GENE ASSEMBLY
    Eugene Oltz; Fiscal Year: 2000
    ..The interactive environment, and diverse expertise offered by Dr. Oltz's colleagues at Vanderbilt, and its Cancer Center, provide an ideal scientific setting to foster these broadened approaches. ..
  17. PROTEOMEWORKSTM SYSTEM
    Richard Cook; Fiscal Year: 2001
    ..For all of these projects, the requested 2-D gel/MALDI-TOF ProteomeWorks(TM) System is essential for accomplishing the stated goals. ..
  18. ASSEMBLY AND EXPRESSION OF IG VARIABLE REGION GENES
    Frederick Alt; Fiscal Year: 2000
    ....
  19. ORGANIZATION AND EXPRESSION OF V GENES
    PETER BRODEUR; Fiscal Year: 2007
    ..We will use a novel cell line model as well as primary bone marrow cells to determine the mechanism through which IL-7 receptor signaling selectively mediates D-distal (5') Vh gene accessibility. ..
  20. SCID MICE AND THE CONTROL OF LYMPHOCYTE DIFFERENTIATION
    MELVIN BOSMA; Fiscal Year: 1993
    ..The experiments outlined in this proposal should tell us more about the effect of SCID on early lymphocyte development. This is important for understanding the genetic control of both normal and abnormal lymphocyte differentiation...
  21. MOLECULAR CONTROL OF ANTIGEN RECEPTOR GENE ASSEMBLY
    Eugene Oltz; Fiscal Year: 2000
    ..Collectively, these studies will yield fundamental insights into the mechanisms that direct, the re-direct recombinase activity to specific antigen receptor loci, and thereby ensure proper lymphocyte development. ..
  22. Protein-DNA Interactions in V(D)J Recombination
    Karla Rodgers; Fiscal Year: 2007
    ..Results from these studies will provide a valuable framework in the determination of the assembly and mechanism of the V(D)J recombinase. ..
  23. DIMINISHED V(D)J RECOMBINATION DURING B CELL DEVELOPMENT
    Rachel Gerstein; Fiscal Year: 2001
    ..This work uses new techniques to study the effect of aging on the immune system and intends, as a long term goal, to identify mechanisms responsible for diminished B cell production in aged mice and humans. ..
  24. New models for RAG-mediated lymphomagenesis
    SANDRA SALUS; Fiscal Year: 2004
    ....
  25. Elements of B Cell Memory
    Marilia Cascalho; Fiscal Year: 2005
    ..memory cell upon engagement by antigen. These goals will be achieved by analysis of the antigen specific Ig titer and by analysis of somatic hypermutation of the heavy-chain V exons following immunization with the cognate antigen. ..
  26. MOLECULAR CONTROL OF ANTIGEN RECEPTOR GENE ASSEMBLY
    Eugene Oltz; Fiscal Year: 2002
    ..studies will resolve a fundamental question in immunology; how do developing lymphocytes regulate choices amongst large arrays of gene segments, any of which could serve as sequence-specific targets for the V(D)J recombinase complex? ..
  27. Control of B Cell Development by Histone Methylation
    LANCE THOMAS; Fiscal Year: 2006
    ..These experiments will reveal the role of G9a in the regulation of B cell maturation, antigen receptor gene assembly, and effector functions in mature B cells. [unreadable] [unreadable] [unreadable]..
  28. V(D)J RECOMBINASE & CHROMOSOME TRANSLOCATION IN LYMPHOMA
    K VANASSE; Fiscal Year: 2003
    ..Such insight may further the understanding of lymphomagenesis and may help in the development of novel anti-tumor strategies. ..
  29. PESTICIDES AND VDJ-RECOMBINASE MUTATIONS IN CHILD NHL
    Jonathan Buckley; Fiscal Year: 2002
    ..The investigators state that the results will be potentially relevant to childhood leukemia as well as lymphoma, and may also have implications for these malignancies in adults. ..
  30. Lymphomagenesis as a Response to Antigenic Stimulation
    SITING STEPHEN CHEN; Fiscal Year: 2002
    ..These studies may improve the understanding of how perturbations in immunity may contribute to NHL. ..
  31. IN VIVO SOMATIC MUTATIONS IN CHILDREN WITH CANCER
    BARRY FINETTE; Fiscal Year: 2001
    ..In addition, the isolation of mutator phenotype clones will allow for future m e chanistic studies characterizing the genetic and biologic defect(s) associated with leukemogenesis in children. ..
  32. IMMUNOGLOBULIN AND T CELL RECEPTOR GENE ASSEMBLY
    David Schatz; Fiscal Year: 2006
    ..Overall, our experiments will address both the targeting and rejoining functions of the RAG proteins, with the long term goal of linking these fundamental activities to chromosomal translocations found in human malignancies. ..
  33. Targeting of somatic hypermutation and gene conversion
    David Schatz; Fiscal Year: 2006
    ..The results of these experiments should set the stage for significant progress toward an understanding of the mechanism by which protein factors and DNA sequences collaborate to target SM and GC to Ig genes. ..
  34. Characterization of V(D)J cleavage and repair complexes
    PATRICK SWANSON; Fiscal Year: 2007
    ..abstract_text> ..
  35. Transcriptional Control of AICDA Expression
    Ferenc Livak; Fiscal Year: 2005
    ..abstract_text> ..
  36. BIOCHEMISTRY AND REGULATION OF V (D) J RECOMBINATION
    Mark Schlissel; Fiscal Year: 2004
    ....
  37. Control Of Tcr Data And Tcr Alpha Rearrangement
    MICHAEL KRANGEL; Fiscal Year: 2005
    ..abstract_text> ..
  38. HUMAN V(D)J RECOMBINASE IN NEOPLASTIC AND PRIMARY CELLS
    Michael Lieber; Fiscal Year: 2004
    ..Corresponding studies of such regions on minichromosomes will permit the testing of the effects of the direction of DNA replication and transcription. ..
  39. c-Abl and PKC-eta in Cell Development and Leukemia
    Mark Schlissel; Fiscal Year: 2008
    ..abstract_text> ..
  40. SOMATIC MUTATIONS IN CHILDREN
    BARRY FINETTE; Fiscal Year: 2002
    ..Results obtained from these studies will provide fundamental insights regarding the clinical relevance of age-specific, spontaneous and environmentally induced somatic mutations in children. ..
  41. REGULATION OF V(D)J RECOMBINATION IN B CELL DEVELOPMENT
    Rachel M Gerstein; Fiscal Year: 2011
    ..abstract_text> ..
  42. Notch signaling in B cell development and survival
    Warren Pear; Fiscal Year: 2002
    ..abstract_text> ..
  43. MDS Nordian Gammacell-40 Exactor Whole Animal Irradiator
    John Monroe; Fiscal Year: 2002
    ..abstract_text> ..
  44. MOLECULAR ANALYSIS OF THE ANTIH INFLUENZAE RESPONSE
    ANN FEENEY; Fiscal Year: 2001
    ..We will also further analyze the diversity in the ani-hib response through the use of combinatorial libraries, correlating affinity with the Vh, Vk and CDR3's which are used. ..
  45. GENETIC PATHWAY TO IGH TRANSLOCATIONS IN LYMPHOMA
    DENNIS WILLERFORD; Fiscal Year: 2003
    ..Ultimately, strategies to prevent lymphoma development in groups at increased risk may emerge. ..
  46. Role of the BCR in B lymphocyte survival and development
    John Monroe; Fiscal Year: 2002
    ....
  47. Intrinsic and extrinsic control of B cells tolerance
    John Monroe; Fiscal Year: 2004
    ..abstract_text> ..
  48. Analyzing VDJ recombination at the single molecule level
    David Roth; Fiscal Year: 2005
    ....
  49. Control of Accessibility for V(D) J Recombination
    ANN FEENEY; Fiscal Year: 2006
    ..We will determine if other transcription factors such as Pax5 or Btk will induce rearrangement of other Ig loci, such as Vh or lambda. ..
  50. Modulatory signaling motifs in B cell antigen receptor function
    Roberta Pelanda; Fiscal Year: 2006
    ..These studies will provide new avenues with which to ameliorate immunodeficiencies, autoimmunities and cancer. ..
  51. Genotoxicity & Emergence of Genome Instability in Humans
    BARRY FINETTE; Fiscal Year: 2007
    ....
  52. The role of AID protein in the host response to viral infection
    F Papavasiliou; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  53. Tolerance in polyclonal and oligoclonal immune systems
    Roberta Pelanda; Fiscal Year: 2007
    ..abstract_text> ..
  54. Receptor Editing in Autoimmune and Normal Mice
    ANN FEENEY; Fiscal Year: 2009
    ..The information gained in these aims should give insights into the response of the various Ig loci to receptor editing signals, and how these processes may potentially be misregulated in B cells of autoimmune mice. ..
  55. B CELL REPERTOIRE FORMATION
    ANN FEENEY; Fiscal Year: 2009
    ..Together, these studies should give insight into the epigenetic mechanisms and cis-elements which control VH gene rearrangement in fetal and adult pro-B cells. ..