Increased frequency of aberrant V(D)J recombination products in core RAG-expressing mice

Nucleic Acids Research

Volumn 32, Issue 15, 2004, Pages 4539-4549

  Talukder, Sadiqur R ^b   Dudley, Darryll D ^a   Alt, Frederick W ^a   Takahama, Yousuke ^b   Akamatsu, Yoshiko ^b,c  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b UNIVERSITY OF TOKUSHIMA   (Japan)

^c PROTEIN DESIGN LABS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CORE PROTEIN; GENOMIC DNA; LYMPHOCYTE ANTIGEN RECEPTOR; OLIGONUCLEOTIDE; RAG1 PROTEIN; RAG2 PROTEIN; SIGNAL PEPTIDE; T LYMPHOCYTE RECEPTOR; DNA BINDING PROTEIN; HOMEODOMAIN PROTEIN; IMMUNOGLOBULIN FRAGMENT; RAG 1 PROTEIN; RAG-1 PROTEIN; RAG2 PROTEIN, MOUSE; V(D)J RECOMBINATION ACTIVATING PROTEIN 2;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; GENE DELETION; GENE EXPRESSION; GENE FREQUENCY; GENE FUNCTION; GENE LOCUS; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC CODE; GENETIC RECOMBINATION; IN VIVO STUDY; KNOCKOUT MOUSE; MOUSE; NONHUMAN; PRIORITY JOURNAL; ANIMAL; CHEMISTRY; GENE; GENE REARRANGEMENT; GENE TARGETING; GENETICS; IMMUNOGLOBULIN STRUCTURE; IMMUNOGLOBULIN VARIABLE REGION; METABOLISM; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE;

ANIMALS; BASE SEQUENCE; DNA-BINDING PROTEINS; GENE REARRANGEMENT; GENE TARGETING; GENES, RAG-1; HOMEODOMAIN PROTEINS; IMMUNOGLOBULIN FRAGMENTS; IMMUNOGLOBULIN JOINING REGION; IMMUNOGLOBULIN VARIABLE REGION; MICE; MOLECULAR SEQUENCE DATA; RECEPTORS, ANTIGEN; SEQUENCE DELETION;

EID: 4344571097     PISSN: 03051048     EISSN: None     Source Type: Journal    
DOI: 10.1093/nar/gkh778     Document Type: Article

References (69)

1. Bassing,C.H., Swat,W. and Alt,F.W. (2002) The mechanism and regulation of chromosomal V(D)J recombination. Cell, 109 (Suppl.), S45-S55.
2. Gellert,M. (2002) V(D)J recombination: RAG proteins, repair factors, and regulation. Annu. Rev. Biochem., 71, 101-132.
3. Agrawal,A. and Schatz,D.G. (1997) RAG1 and RAG2 form a stable postcleavage synaptic complex with DNA containing signal ends in V(D)J recombination. Cell, 89, 43-53.
4. Hiom,K. and Gellert,M. (1998) Assembly of a 12/23 paired signal complex: a critical control point in V(D)J recombination. Mol. Cell, 1, 1011-1019.
5. Jones,J.M. and Gellert,M. (2001) Intermediates in V(D)J recombination: a stable RAG1/2 complex sequesters cleaved RSS ends. Proc. Natl Acad. Sci. USA, 98, 12926-12931.
6. Brandt,V.L. and Roth,D.B. (2002) A recombinase diversified: new functions of the RAG proteins. Curr. Opin. Immunol., 14, 224-229.
7. Dai,Y., Kysela,B., Hanakahi,L.A., Manolis,K., Riballo,E., Stumm,M., Harville,T.O., West,S.C., Oettinger,M.A. and Jeggo,P.A. (2003) Nonhomologous end joining and V(D)J recombination require an additional factor. Proc. Natl Acad. Sci. USA, 100, 2462-2467.
8. Cuomo,C.A. and Oettinger,M.A. (1994) Analysis of regions of RAG-2 important for V(D)J recombination. Nucleic Acids Res., 22, 1810-1814.
9. Kirch,S.A., Sudarsanam,P. and Oettinger,M.A. (1996) Regions of RAG1 protein critical for V(D)J recombination. Eur. J. Immunol., 26, 886-891.
10. Sadofsky,M.J., Hesse,J.E., McBlane,J.F. and Gellert,M. (1993) Expression and V(D)J recombination activity of mutated RAG-1 proteins. Nucleic Acids Res., 21, 5644-5650.
11. Sadofsky,M.J., Hesse,J.E. and Gellert,M. (1994) Definition of a core region of RAG-2 that is functional in V(D)J recombination. Nucleic Acids Res., 22, 1805-1809.
12. Silver,D.P., Spanopoulou,E., Mulligan,R.C. and Baltimore,D. (1993) Dispensable sequence motifs in the RAG-1 and RAG-2 genes for plasmid V(D)J recombination. Proc. Natl Acad. Sci. USA, 90, 6100-6104.
13. Elkin,S.K., Matthews,A.G. and Oettinger,M.A. (2003) The C-terminal portion of RAG2 protects against transposition in vitro. EMBO J., 22, 1931-1938.
14. Melek,M. and Gellert,M. (2000) RAG1/2-mediated resolution of transposition intermediates: two pathways and possible consequences. Cell, 101, 625-633.
15. Sekiguchi,J.A., Whitlow,S. and Alt,F.W. (2001) Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGs. Mol. Cell, 8, 1383-1390.
16. Swanson,P.C., Volkmer,D. and Wang,L. (2004) Full-length RAG-2, and not full-length RAG1, specifically suppresses RAG-mediated transposition, but not hybrid joint formation or disintegration. J. Biol. Chem., 279, 4034-4044.
17. Tsai,C.L. and Schatz,D.G. (2003) Regulation of RAG1/RAG2-mediated transposition by GTP and the C-terminal region of RAG2. EMBO J., 22, 1922-1930.
18. Jones,J.M. and Gellert,M. (2003) Autoubiquitylation of the V(D)J recombinase protein RAG1. Proc. Natl Acad. Sci. USA, 100, 15446-15451.
19. Lee,J. and Desiderio,S. (1999) Cyclin A/CDK2 regulates V(D)J recombination by coordinating RAG-2 accumulation and DNA repair. Immunity, 11, 771-781.
20. Yurchenko,V., Xue,Z. and Sadofsky,M. (2003) The RAG1 N-terminal domain is an E3 ubiquitin ligase. Genes Dev., 17, 581-585.
21. Corneo,B., Benmerah,A. and Villartay,J.P. (2002) A short peptide at the C-terminus is responsible for the nuclear localization of RAG2. Eur. J. Immunol., 32, 2068-2073.
22. Spanopoulou,E., Cortes,P., Shih,C., Huang,C.M., Silver,D.P., Svec,P. and Baltimore,D. (1995) Localization, interaction, and RNA binding properties of the V(D)J recombination-activating proteins RAG1 and RAG2. Immunity, 3, 715-726.
23. Akamatsu,Y., Monroe,R., Dudley,D.D., Elkin,S.K., Gartner,F., Talukder,S.R., Takahama,Y., Alt,F.W., Bassing,C.H. and Oettinger,M.A. (2003) Deletion of the RAG2 C-terminus leads to impaired lymphoid development in mice. Proc. Natl Acad. Sci. USA, 100, 1209-1214.
24. Dudley,D.D., Sekiguchi,J., Zhu,C., Sadofsky,M.J., Whitlow,S., DeVido,J., Monroe,R.J., Bassing,C.H. and Alt,F.W. (2003) Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice. J. Exp. Med., 198, 1439-1450.
25. Liang,H.E., Hsu,L.Y., Cado,D., Cowell,L.G., Kelsoe,G. and Schlissel,M.S. (2002) The 'dispensable' portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development. Immunity, 17, 639-651.
26. Villa,A., Sobacchi,C., Notarangeto,L.D., Bozzi,F., Abinun,M., Abrahamsen,T.G., Arkwright,P.D., Baniyash,M., Brooks,E.G., Conley,M.E. et al. (2001) V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations. Blood, 97, 81-88.
27. Steen,S.B., Han,J.O., Mundy,C., Oettinger,M.A. and Roth,D.B. (1999) Roles of the 'dispensable' portions of RAG-1 and RAG-2 in V(D)J recombination. Mol. Cell Biol., 19, 3010-3017.
28. Qiu,J.X., Kale,S.B., Yarnell Schultz,H. and Roth,D.B. (2001) Separation-of-function mutants reveal critical roles for RAG2 in both the cleavage and joining steps of V(D)J recombination. Mol. Cell, 7, 77-87.
29. Yarnell Schultz,H., Landree,M.A., Qiu,J.X., Kale,S.B. and Roth,D.B. (2001) Joining-deficient RAG1 mutants block V(D)J recombination in vivo and hairpin opening in vitro. Mol. Cell, 7, 65-75.
30. Tsai,C.L., Drejer,A.H. and Schatz,D.G. (2002) Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination. Genes Dev., 16, 1934-1949.
31. Huye,L.E., Purugganan,M.M., Jiang,M.M. and Roth,D.B. (2002) 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. Mol. Cell Biol., 22, 3460-3473.
32. Miller,S.A., Dykes,D.D. and Polesky,H.F. (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res., 16, 1215.
33. Lewis,S.M. (1994) The mechanism of V(D)J joining: lessons from molecular, immunological, and comparative analyses. Adv. Immunol., 56, 27-150.
34. Starr,T.K., Jameson,S.C. and Hogquist,K.A. (2003) Positive and negative selection of T cells. Annu. Rev. Immunol., 21, 139-176.
35. Clatworthy,A.E., Valencia,M.A., Haber,J.E. and Oettinger,M.A. (2003) V(D)J recombination and RAG-mediated transposition in yeast. Mol. Cell, 12, 489-499.
36. Kanaar,R., Hoeijmakers,J.H.J. and van Gent,D.C. (1998) Molecular mechanisms of DNA double-strand break repair. Trends Cell Biol., 8, 483-489.
37. Baumann,P. and West,S.C. (1998) DNA end-joining catalyzed by human cell-free extracts. Proc. Natl Acad. Sci. USA, 95, 14066-14070.
38. Kabotyanski,E.B., Gomelsky,L., Han,J.O., Stamato,T.D. and Roth,D.B. (1998) Double-strand break repair in Ku86- and XRCC4-deficient cells. Nucleic Acids Res., 26, 5333-5342.
39. Verkaik,N.S., Esveldt-van Lange,R.E., van Heemst,D., Bruggenwirth,H.T., Hoeijmakers,J.H., Zdzienicka,M.Z. and van Gent,D.C. (2002) Different types of V(D)J recombination and end-joining defects in DNA double-strand break repair mutant mammalian cells. Eur. J. Immunol., 32, 701-709.
40. Roth,D.B. (2003) Restraining the V(D)J recombinase. Nature Rev. Immunol., 3, 656-666.
41. Li,Z., Otevrel,T., Gao,Y., Cheng,H.L., Seed,B., Stamato,T.D., Taccioli,G.E. and Alt,F.W. (1995) The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination. Cell, 83, 1079-1089.
42. Roth,D.B., Proctor,G.N., Stewart,L.K. and Wilson,J.H. (1991) Oligonucleotide capture during end joining in mammalian cells. Nucleic Acids Res., 19, 7201-7205.
43. Lieber,M.R. (1992) The mechanism of V(D)J recombination: a balance of diversity, specificity, and stability. Cell, 70, 873-876.
44. Lieber,M.R., Hesse,J.E., Lewis,S., Bosma,G.C., Rosenberg,N., Mizuuchi,K., Bosma,M.J. and Gellert,M. (1988) The defect in marine severe combined immune deficiency: joining of signal sequences but nop coding segments in V(D)J recombination. Cell, 55, 7-16.
45. Schuler,W., Ruetsch,N.R., Amsler,M. and Bosma,M.J. (1991) Coding joint formation of endogenous T cell receptor genes in lymphoid cells from scid mice: unusual P-nucleotide additions in VJ-coding joints. Eur. J. Immunol., 21, 589-596.
46. Carroll,A.M., Slack,J.K. and Mu,X. (1993) V(D)J recombination generates a high frequency of nonstandard TCR D delta-associated rearrangements in thymocytes. J. Immunol., 150, 2222-2230.
47. Ramsden,D.A., McBlane,J.F., van Gent,D.C. and Gellert,M. (1996) Distinct DNA sequence and structure requirements for the two steps of V(D)J recombination signal cleavage. EMBO J., 15, 3197-3206.
48. Cuomo,C.A., Mundy,C.L. and Oettinger,M.A. (1996) DNA sequence and structure requirements for cleavage of V(D)J recombination signal sequences. Mol. Cell Biol., 16, 5683-5690.
49. Tycko,B. and Sklar,J. (1990) Chromosomal translocations in lymphoid neoplasia: a reappraisal of the recombinase model. Cancer Cells, 2, 1-8.
50. Jones,J.M. and Gellert,M. (2002) Ordered assembly of the V(D)J synaptic complex ensures accurate recombination. EMBO J., 21, 4162-4171.
51. Mundy,C.L., Patenge,N., Matthews,A.G. and Oettinger,M.A. (2002) Assembly of the RAG1/RAG2 synaptic complex. Mol. Cell Biol., 22, 69-77.
52. Raghavan,S.C., Swanson,P.C., Wu,X., Hsieh,C.L. and Lieber,M.R. (2004) A non-B-DNA structure at the Bcl-2 major breakpoint region is cleaved by the RAG complex. Nature, 428, 88-93.
53. Nagawa,F., Hirose,S., Nishizumi,H., Nishihara,T. and Sakano,H. (2004) Joining mutants of RAG1 and RAG2 demonstrate impaired interactions with the coding-end DNA. J. Biol. Chem. [Epub ahead of print].
54. Sleckman,B.P., Bassing,C.H., Hughes,M.M., Okada,A., D'Auteuil,M., Wehrly,T.D., Woodman,B.B., Davidson,L., Chen,J. and Alt,F.W. (2000) Mechanisms that direct ordered assembly of T cell receptor beta locus V, D, and J gene segments. Proc. Natl Acad. Sci. USA, 97, 7975-7980.
55. Bassing,C.H., Alt,F.W., Hughes,M.M., D'Auteuil,M., Wehrly,T.D., Woodman,B.B., Gartner,F., White,J.M., Davidson,L. and Sleckman,B.P. (2000) Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule. Nature, 405, 583-586.
56. Montalbano,A., Ogwaro,K.M., Tang,A., Matthews,A.G., Larijani,M., Oettinger,M.A. and Feeney,A.J. (2003) V(D)J recombination frequencies can be profoundly affected by changes in the spacer sequence. J. Immunol., 171, 5296-5304.
57. Lee,A.I., Fugmann,S.D., Cowell,L.G., Ptaszek,L.M., Kelsoe,G. and Schatz,D.G. (2003) A functional analysis of the spacer of V(D)J recombination signal sequences. PLoS Biol., 1, 56-69.
58. Lee,G.S., Neiditch,M.B., Salus,S.S. and Roth,D.B. (2004) RAG proteins shepherd double-strand breaks to a specific pathway, suppressing error-prone repair, but RAG nicking initiates homologous recombination. Cell, 117, 171-184.
59. Fugmann,S.D., Villey,I.J., Ptaszek,L.M. and Schatz,D.G. (2000) Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complex. Mol. Cell, 5, 97-107.
60. Fugmann,S.D. and Schatz,D.G. (2001) Identification of basic residues in RAG2 critical for DNA binding by the RAG1-RAG2 complex. Mol. Cell, 8, 899-910.
61. Purugganan,M.M., Shah,S., Kearney,J.F. and Roth,D.B. (2001) Ku80 is required for addition of N nucleotides to V(D)J recombination junctions by terminal deoxynucleotidyl transferase. Nucleic Acids Res., 29, 1638-1646.
62. Yu,K., Taghva,A. and Lieber,M.R. (2002) The cleavage efficiency of the human immunoglobulin heavy chain VH elements by the RAG complex. J. Biol. Chem., 277, 5040-5046.
63. Olaru,A., Patterson,D.N., Villey,I. and Livak,F. (2003) DNA-Rag protein interaction in the control of selective D gene utilization in the TCR beta locus. J. Immunol., 171, 3605-3611.
64. Gerstein,R.M. and Lieber,M.R. (1993) Coding end sequence can markedly affect the initiation of V(D)J recombination. Genes Dev., 7, 1459-1469.
65. Eastman,Q.M., Villey,I.J. and Schatz,D.G. (1999) Detection of RAG protein-V(D)J recombination signal interactions near the site of DNA cleavage by UV cross-linking. Mol. Cell Biol., 19, 3788-3797.
66. Mo,X., Bailin,T. and Sadofsky,M.J. (2001) A C-terminal region of RAG1 contacts the coding DNA during V(D)J recombination. Mol. Cell Biol., 21, 2038-2047.
67. Yu,K. and Lieber,M.R. (1999) Mechanistic basis for coding end sequence effects in the initiation of V(D)J recombination. Mol. Cell Biol., 19, 8094-8102.
68. Jung,D., Bassing,C.H., Fugmann,S.D., Cheng,H.L., Schatz,D.G. and Alt,F.W. (2003) Extrachromosomal recombination substrates recapitulate beyond 12/23 restricted VDJ recombination in nonlymphoid cells. Immunity, 18, 65-74.
69. Livak,F., Burtrum,D.B., Rowen,L., Schatz,D.G. and Petrie,H.T. (2000) Genetic modulation of T cell receptor gene segment usage during somatic recombination. J. Exp. Med., 192, 1191-1196.