Early Steps of V(D)J Rearrangement: Insights from Biochemical Studies of RAG-RSS Complexes

  • Patrick C. Swanson
  • Sushil Kumar
  • Prafulla Raval
Part of the Advances in Experimental Medicine and Biology book series (volume 650)


V(D)J recombination is initiated by the synapsis and cleavage of a complementary (12/23) pair of recombination signal sequences (RSSs) by the RAG1 and RAG2 proteins. Our understanding of these processes has been greatly aided by the development of in vitro biochemical assays of RAG binding and cleavage activity. Accumulating evidence suggests that synaptic complex assembly occurs in a step-wise manner and that the RAG proteins catalyze RSS cleavage by mechanisms similar to those used by bacterial transposases. In this chapter we will review the molecular mechanisms of RAG synaptic complex assembly and 12/23-regulated RSS cleavage, focusing on recent advances that shed new light on these processes.


Recombination Signal Recombination Signal Sequence Synaptic Complex Hairpin Formation Code Flank 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Bassing CH, Swat W, Alt FW. The mechanism and regulation of chromosomal V(D)J recombination. Cell 2002; 109(Suppl):S45–55.Google Scholar
  2. 2.
    Ramsden DA, Baetz K, Wu GE. Conservation of sequence in recombination signal sequence spacers. Nucleic Acids Res 1994; 22(10):1785–1796.PubMedGoogle Scholar
  3. 3.
    Schatz DG, Oettinger MA, Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell 1989; 59(6):1035–1048.PubMedGoogle Scholar
  4. 4.
    Oettinger MA, Schatz DG, Gorka C et al. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination. Science 1990; 248(4962):1517–1523.PubMedGoogle Scholar
  5. 5.
    Gellert M. V(D)J recombination: RAG proteins, repair factors and regulation. Annu Rev Biochem 2002; 71:101–132.PubMedGoogle Scholar
  6. 6.
    Fugmann SD, Lee AI, Shockett PE et al. The RAG proteins and V(D)J recombination: complexes, ends and transposition. Annu Rev Immunol 2000; 18:495–527.PubMedGoogle Scholar
  7. 7.
    Schlissel M, Constantinescu A, Morrow T et al. Double-strand signal sequence breaks in V(D)J recombination are blunt, 5′-phosphorylated, RAG-dependent and cell cycle regulated. Genes Dev 1993; 7(12B):2520–2532.PubMedGoogle Scholar
  8. 8.
    Roth DB, Menetski JP, Nakajima PB et al. V(D)J recombination: broken DNA molecules with covalently sealed (hairpin) coding ends in scid mouse thymocytes. Cell 1992; 70(6):983–991.PubMedGoogle Scholar
  9. 9.
    McBlane JF, van Gent DC, Ramsden DA et al. Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell 1995; 83(3):387–395.PubMedGoogle Scholar
  10. 10.
    Lewis SM, Hesse JE, Mizuuchi K et al. Novel strand exchanges in V(D)J recombination. Cell 1988; 55(6):1099–1107.PubMedGoogle Scholar
  11. 11.
    Morzycka-Wroblewska E, Lee FE, Desiderio SV. Unusual immunoglobulin gene rearrangement leads to replacement of recombinational signal sequences. Science 1988; 242(4876):261–263.PubMedGoogle Scholar
  12. 12.
    Lieber MR, Ma Y, Pannicke U et al. The mechanism of vertebrate nonhomologous DNA end joining and its role in V(D)J recombination. DNA Repair (Amst) 2004; 3(8–9):817–826.Google Scholar
  13. 13.
    Buck D, Malivert L, de Chasseval R et al. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell 2006; 124(2):287–299.PubMedGoogle Scholar
  14. 14.
    Ahnesorg P, Smith P, Jackson SP. XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 2006; 124(2):301–313.PubMedGoogle Scholar
  15. 15.
    Ma Y, Pannicke U, Schwarz K et al. Hairpin opening and overhang processing by an artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell 2002; 108(6):781–794.PubMedGoogle Scholar
  16. 16.
    Bertocci B, De Smet A, Berek C et al. Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu. Immunity 2003; 19(2):203–211.PubMedGoogle Scholar
  17. 17.
    Bertocci B, De Smet A, Weill JC et al. Nonoverlapping functions of DNA polymerases mu, lambda and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo. Immunity 2006; 25(1):31–41.PubMedGoogle Scholar
  18. 18.
    Weterings E, Chen DJ. The endless tale of nonhomologous end-joining. Cell Res 2008;18(1):114–124.PubMedGoogle Scholar
  19. 19.
    Rooney S, Chaudhuri J, Alt FW. The role of the nonhomologous end-joining pathway in lymphocyte development. Immunol Rev 2004; 200:115–131.PubMedGoogle Scholar
  20. 20.
    Lieber MR, Lu H, Gu J et al. Flexibility in the order of action and in the enzymology of the nuclease, polymerases and ligase of vertebrate nonhomologous DNA end joining: relevance to cancer, aging and the immune system. Cell Res 2008; 18(1):125–133.PubMedGoogle Scholar
  21. 21.
    De P, Rodgers KK. Putting the pieces together: identification and characterization of structural domains in the V(D)J recombination protein RAG1. Immunol Rev 2004; 200:70–82.PubMedGoogle Scholar
  22. 22.
    Eastman QM, Leu TM, Schatz DG. Initiation of V(D)J recombination in vitro obeying the 12/23 rule. Nature 1996; 380(6569):85–88.PubMedGoogle Scholar
  23. 23.
    van Gent DC, Ramsden DA, Gellert M. The RAG1 and RAG2 proteins establish the 12/23 rule in V(D)J recombination. Cell 1996; 85(1):107–113.PubMedGoogle Scholar
  24. 24.
    Swanson PC. The bounty of RAGs: recombination signal complexes and reaction outcomes. Immunol Rev 2004; 200:90–114.PubMedGoogle Scholar
  25. 25.
    Difilippantonio MJ, McMahan CJ, Eastman QM et al. RAG1 mediates signal sequence recognition and recruitment of RAG2 in V(D)J recombination. Cell 1996; 87(2):253–262.PubMedGoogle Scholar
  26. 26.
    Spanopoulou E, Zaitseva F, Wang FH et al. The homeodomain region of Rag-1 reveals the parallel mechanisms of bacterial and V(D)J recombination. Cell 1996; 87(2):263–276.PubMedGoogle Scholar
  27. 27.
    Swanson PC, Desiderio S. RAG-2 promotes heptamer occupancy by RAG-1 in the assembly of a V(D)J initiation complex. Mol Cell Biol 1999; 19(5):3674–3683.PubMedGoogle Scholar
  28. 28.
    Ciubotaru M, Ptaszek LM, Baker GA et al. RAG1-DNA binding in V(D)J recombination. Specificity and DNA-induced conformational changes revealed by fluorescence and CD spectroscopy. J Biol Chem 2003; 278(8):5584–5596.PubMedGoogle Scholar
  29. 29.
    Bailin T, Mo X, Sadofsky MJ. A RAG1 and RAG2 tetramer complex is active in cleavage in V(D)J recombination. Mol Cell Biol 1999; 19(7):4664–4671.PubMedGoogle Scholar
  30. 30.
    Rodgers KK, Villey IJ, Ptaszek L et al. A dimer of the lymphoid protein RAG1 recognizes the recombination signal sequence and the complex stably incorporates the high mobility group protein HMG2. Nucleic Acids Res 1999; 27(14):2938–2946.PubMedGoogle Scholar
  31. 31.
    Godderz LJ, Rahman NS, Risinger GM et al. Self-association and conformational properties of RAG1: implications for formation of the V(D)J recombinase. Nucleic Acids Res 2003; 31(7):2014–2023.PubMedGoogle Scholar
  32. 32.
    Swanson PC, Desiderio S. V(D)J recombination signal recognition distinct, overlapping DNA-protein contacts in complexes containing RAG1 with and without RAG2. Immunity 1998; 9(1):115–125.PubMedGoogle Scholar
  33. 33.
    Hiom K, Gellert M. A stable RAG1-RAG2-DNA complex that is active in V(D)J cleavage. Cell 1997; 88(1):65–72.PubMedGoogle Scholar
  34. 34.
    Mundy CL, Patenge N, Matthews AG et al. Assembly of the RAG1/RAG2 synaptic complex. Mol Cell Biol 2002; 22(1):69–77.PubMedGoogle Scholar
  35. 35.
    Santagata S, Aidinis V, Spanopoulou E. The effect of Me2+ cofactors at the initial stages of V(D)J recombination. J Biol Chem 1998; 273(26):16325–16331.PubMedGoogle Scholar
  36. 36.
    Mo X, Bailin T, Sadofsky MJ. RAG1 and RAG2 cooperate in specific binding to the recombination signal sequence in vitro. J Biol Chem 1999; 274(11):7025–7031.PubMedGoogle Scholar
  37. 37.
    Swanson PC. A RAG-1/RAG-2 tetramer supports 12/23-regulated synapsis, cleavage and transposition of V(D)J recombination signals. Mol Cell Biol 2002; 22(22):7790–7801.PubMedGoogle Scholar
  38. 38.
    Raval P, Kriatchko AN, Kumar S et al. Evidence for Ku70/Ku80 association with full-length RAG1. Nucleic Acids Res 2008; 36(6):2060–2072.PubMedGoogle Scholar
  39. 39.
    De P, Zhao S, Gwyn LM et al. Thermal dependency of RAG1 self-association properties. BMC Biochem 2008; 9:5.PubMedGoogle Scholar
  40. 40.
    Kim DR, Dai Y, Mundy CL et al. Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase. Genes Dev 1999; 13(23):3070–3080.PubMedGoogle Scholar
  41. 41.
    Landree MA, Wibbenmeyer JA, Roth DB. Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination. Genes Dev 1999; 13(23):3059–3069.PubMedGoogle Scholar
  42. 42.
    Fugmann SD, Villey IJ, Ptaszek LM et al. Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complex. Mol Cell 2000; 5(1):97–107.PubMedGoogle Scholar
  43. 43.
    Haren L, Ton-Hoang B, Chandler M. Integrating DNA: transposases and retroviral integrases. Annu Rev Microbiol 1999; 53:245–281.PubMedGoogle Scholar
  44. 44.
    Davies DR, Goryshin IY, Reznikoff WS et al. Three-dimensional structure of the Tn5 synaptic complex transposition intermediate. Science 2000; 289(5476):77–85.PubMedGoogle Scholar
  45. 45.
    Naumann TA, Reznikoff WS. Trans catalysis in Tn5 transposition. Proc Natl Acad Sci USA 2000; 97(16):8944–8949.PubMedGoogle Scholar
  46. 46.
    Landree MA, Kale SB, Roth DB. Functional organization of single and paired V(D)J cleavage complexes. Mol Cell Biol 2001; 21(13):4256–4264.PubMedGoogle Scholar
  47. 47.
    Swanson PC. The DDE motif in RAG-1 is contributed in trans to a single active site that catalyzes the nicking and transesterification steps of V(D)J recombination. Mol Cell Biol 2001; 21(2):449–458.PubMedGoogle Scholar
  48. 48.
    van Gent DC, Hiom K, Paull TT et al. Stimulation of V(D)J cleavage by high mobility group proteins. EMBO J 1997; 16(10):2665–2670.PubMedGoogle Scholar
  49. 49.
    Sawchuk DJ, Weis-Garcia F, Malik S et al. V(D)J recombination: modulation of RAG1 and RAG2 cleavage activity on 12/23 substrates by whole cell extract and DNA-bending proteins. J Exp Med 1997; 185(11):2025–2032.PubMedGoogle Scholar
  50. 50.
    Calogero S, Grassi F, Aguzzi A et al. The lack of chromosomal protein hmgl does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice. Nat Genet 1999; 22(3):276–280.PubMedGoogle Scholar
  51. 51.
    Swanson PC. Fine structure and activity of discrete RAG-HMG complexes on V(D)J recombination signals. Mol Cell Biol 2002; 22(5):1340–1351.PubMedGoogle Scholar
  52. 52.
    Thomas JO, Travers AA. HMG1 and 2 and related ‘architectural’ DNA-binding proteins. Trends Biochem Sci 2001; 26(3):167–174.PubMedGoogle Scholar
  53. 53.
    Klune JR, Dhupar R, Cardinal J et al. Hmgb1: Endogenous danger signaling. Mol Med 2008; 14(7–8):476–484.PubMedGoogle Scholar
  54. 54.
    Aidinis V, Bonaldi T, Beltrame M et al. The RAG1 homeodomain recruits HMG1 and HMG2 to facilitate recombination signal sequence binding and to enhance the intrinsic DNA-bending activity of RAG1–RAG2. Mol Cell Biol 1999; 19(10):6532–6542.PubMedGoogle Scholar
  55. 55.
    Yoshida T, Tsuboi A, Ishiguro K et al. The DNA-bending protein, HMG1, is required for correct cleavage of 23 bp recombination signal sequences by recombination activating gene proteins in vitro. Int Immunol 2000; 12(5):721–729.PubMedGoogle Scholar
  56. 56.
    Bergeron S, Madathiparambil T, Swanson PC. Both high mobility group (HMG)-boxes and the acidic tail of HMGB1 regulate recombination-activating gene (RAG)-mediated recombination signal synapsis and cleavage in vitro. J Biol Chem 2005; 280(35):31314–31324.PubMedGoogle Scholar
  57. 57.
    Kriatchko AN, Bergeron S, Swanson PC. HMG-box domain stimulation of RAG1/2 cleavage activity is metal ion dependent. BMC Mol Biol 2008; 9:32.PubMedGoogle Scholar
  58. 58.
    Dai Y, Wong B, Yen YM et al. Determinants of HMGB proteins required to promote RAG1/2-recombination signal sequence complex assembly and catalysis during V(D)J recombination. Mol Cell Biol 2005; 25(11):4413–4425.PubMedGoogle Scholar
  59. 59.
    Bonaldi T, Langst G, Strohner R et al. The DNA chaperone HMGB1 facilitates ACF/CHRAC-dependent nucleosome sliding. EMBO J 2002; 21(24):6865–6873.PubMedGoogle Scholar
  60. 60.
    Ueda T, Chou H, Kawase T et al. Acidic C-tail of HMGB1 is required for its target binding to nucleosome linker DNA and transcription stimulation. Biochemistry 2004; 43(30):9901–9908.PubMedGoogle Scholar
  61. 61.
    Kwon J, Imbalzano AN, Matthews A et al. Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1. Mol Cell 1998; 2(6):829–839.PubMedGoogle Scholar
  62. 62.
    Nightingale KP, Baumann M, Eberharter A et al. Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination. Nucleic Acids Res 2007; 35(18):6311–6321.PubMedGoogle Scholar
  63. 63.
    Baumann M, Mamais A, McBlane F et al. Regulation of V(D)J recombination by nucleosome positioning at recombination signal sequences. EMBO J 2003; 22(19):5197–5207.PubMedGoogle Scholar
  64. 64.
    Jones JM, Gellert M. Ordered assembly of the V(D)J synaptic complex ensures accurate recombination. EMBO J 2002; 21(15):4162–4171.PubMedGoogle Scholar
  65. 65.
    Curry JD, Geier JK, Schlissel MS. Single-strand recombination signal sequence nicks in vivo: evidence for a capture model of synapsis. Nat Immunol 2005; 6(12):1272–1279.PubMedGoogle Scholar
  66. 66.
    Eastman QM, Schatz DG. Nicking is asynchronous and stimulated by synapsis in 12/23 rule-regulated V(D)J cleavage. Nucleic Acids Res 1997; 25(21):4370–4378.PubMedGoogle Scholar
  67. 67.
    Yu K, Lieber MR. The nicking step in V(D)J recombination is independent of synapsis: implications for the immune repertoire. Mol Cell Biol 2000;20(21):7914–7921.PubMedGoogle Scholar
  68. 68.
    Sheehan KM, Lieber MR. V(D)J recombination: signal and coding joint resolution are uncoupled and depend on parallel synapsis of the sites. Mol Cell Biol 1993; 13(3):1363–1370.PubMedGoogle Scholar
  69. 69.
    Ciubotaru M, Kriatchko AN, Swanson PC et al. Fluorescence resonance energy transfer analysis of recombination signal sequence configuration in the RAG1/2 synaptic complex. Mol Cell Biol 2007; 27(13):4745–4758.PubMedGoogle Scholar
  70. 70.
    Nagawa F, Ishiguro K, Tsuboi A et al. Footprint analysis of the RAG protein recombination signal sequence complex for V(D)J type recombination. Mol Cell Biol 1998; 18(1):655–663.PubMedGoogle Scholar
  71. 71.
    Akamatsu Y, Oettinger MA. Distinct roles of RAG1 and RAG2 in binding the V(D)J recombination signal sequences. Mol Cell Biol 1998; 18(8):4670–4678.PubMedGoogle Scholar
  72. 72.
    Eastman QM, Villey IJ, Schatz DG. Detection of RAG protein-V(D)J recombination signal interactions near the site of DNA cleavage by UV cross-linking. Mol Cell Biol 1999; 19(5):3788–3797.PubMedGoogle Scholar
  73. 73.
    Mo X, Bailin T, Noggle S et al. A highly ordered structure in V(D)J recombination cleavage complexes is facilitated by HMGI. Nucleic Acids Res 2000; 28(5):1228–1236.PubMedGoogle Scholar
  74. 74.
    Nagawa F, Kodama M, Nishihara T et al. Footprint analysis of recombination signal sequences in the 12/23 synaptic complex of V(D)J recombination. Mol Cell Biol 2002; 22(20):7217–7225.PubMedGoogle Scholar
  75. 75.
    Nagawa F, Hirose S, Nishizumi H et al. Joining mutants of RAG1 and RAG2 that demonstrate impaired interactions with the coding-end DNA. J Biol Chem 2004; 279(37):38360–38368.PubMedGoogle Scholar
  76. 76.
    Tsai CL, Drejer AH, Schatz DG. 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(15):1934–1949.PubMedGoogle Scholar
  77. 77.
    Qiu JX, Kale SB, Yarnell Schultz H et al. Separation-of-function mutants reveal critical roles for RAG2 in both the cleavage and joining steps of V(D)J recombination. Mol Cell 2001; 7(1):77–87.PubMedGoogle Scholar
  78. 78.
    Cuomo CA, Mundy CL, Oettinger MA. DNA sequence and structure requirements for cleavage of V(D)J recombination signal sequences. Mol Cell Biol 1996; 16(10):5683–5690.PubMedGoogle Scholar
  79. 79.
    Ramsden DA, McBlane JF, van Gent DC et al. Distinct DNA sequence and structure requirements for the two steps of V(D)J recombination signal cleavage. EMBO J 1996; 15(12):3197–3206.PubMedGoogle Scholar
  80. 80.
    Grundy GJ, Hesse JE, Gellert M. Requirements for DNA hairpin formation by RAG1/2. Proc Natl Acad Sci USA 2007; 104(9):3078–3083.PubMedGoogle Scholar
  81. 81.
    Bhasin A, Goryshin IY, Reznikoff WS. Hairpin formation in Tn5 transposition. J Biol Chem 1999; 274(52):3702–37029.Google Scholar
  82. 82.
    Nishihara T, Nagawa F, Imai T et al. RAG-heptamer interaction in the synaptic complex is a crucial biochemical checkpoint for the 12/23 recombination rule. J Biol Chem 2008; 283(8):4877–4885.PubMedGoogle Scholar
  83. 83.
    Ason B, Reznikoff WS. Mutational analysis of the base flipping event found in Tn5 transposition. J Biol Chem 2002; 277(13):11284–11291.PubMedGoogle Scholar
  84. 84.
    Bischerour J, Chalmers R. Base-flipping dynamics in a DNA hairpin processing reaction. Nucleic Acids Res 2007; 35(8):2584–2595.PubMedGoogle Scholar
  85. 85.
    Lu CP, Sandoval H, Brandt VL et al. Amino acid residues in rag1 crucial for DNA hairpin formation. Nat Struct Mol Biol 2006; 13(11):1010–1015.PubMedGoogle Scholar
  86. 86.
    Bergeron S, Anderson DK, Swanson PC. RAG and HMGB1 proteins: purification and biochemical analysis of recombination signal complexes. Methods Enzymol 2006; 408:511–528.PubMedGoogle Scholar
  87. 87.
    Kriatchko AN, Anderson DK, Swanson PC. Identification and characterization of a gain-of-function RAG-1 mutant. Mol Cell Biol 2006; 26(12):4712–4728.PubMedGoogle Scholar
  88. 88.
    Ciubotaru M, Schatz DG. Synapsis of recombination signal sequences located in cis and DNA underwinding in V(D)J recombination. Mol Cell Biol 2004; 24(19):8727–8744.PubMedGoogle Scholar
  89. 89.
    Schatz DG. V(D)J recombination moves in vitro. Semin Immunol 1997; 9(3):149–159.PubMedGoogle Scholar
  90. 90.
    West KL, Singha NC, De Ioannes P et al. A direct interaction between the RAG2 C terminus and the core histones is required for efficient V(D)J recombination. Immunity 2005; 23(2):203–212.PubMedGoogle Scholar
  91. 91.
    Liu Y, Subrahmanyam R, Chakraborty T et al. A plant homeodomain in RAG-2 that binds hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement. Immunity 2007; 27(4):561–571.PubMedGoogle Scholar
  92. 92.
    Matthews AG, Kuo AJ, Ramon-Maiques S et al. RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature 2007; 450(7172):1106–1110.PubMedGoogle Scholar
  93. 93.
    Zhang Z, Espinoza CR, Yu Z et al. Transcription factor pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes. Nat Immunol 2006; 7(6):616–624.PubMedGoogle Scholar
  94. 94.
    Wang X, Xiao G, Zhang Y et al. Regulation of tcrb recombination ordering by c-fos-dependent RAG deposition. Nat Immunol 2008; 9(7):794–801.PubMedGoogle Scholar
  95. 95.
    Cobaleda C, Schebesta A, Delogu A et al. Pax5: the guardian of B-cell identity and function. Nat Immunol 2007; 8(5):463–470.PubMedGoogle Scholar
  96. 96.
    Jackson AM, Krangel MS. Turning T-cell receptor beta recombination on and off: more questions than answers. Immunol Rev 2006; 209:129–141.PubMedGoogle Scholar
  97. 97.
    Chen L, Glover JN, Hogan PG et al. Structure of the DNA-binding domains from NFAT, fos and jun bound specifically to DNA. Nature 1998; 392(6671):42–48.PubMedGoogle Scholar
  98. 98.
    Jones JM, Gellert M. The taming of a transposon: V(D)J recombination and the immune system. Immunol Rev 2004; 200:233–248.PubMedGoogle Scholar
  99. 99.
    Feeney AJ, Tang A, Ogwaro KM. B-cell repertoire formation: role of the recombination signal sequence in nonrandom V segment utilization. Immunol Rev 2000; 175:59–69.PubMedGoogle Scholar
  100. 100.
    Livak F, Burtrum DB, Rowen L et al. Genetic modulation of T-cell receptor gene segment usage during somatic recombination. J Exp Med 2000; 192(8):1191–1196.PubMedGoogle Scholar
  101. 101.
    Ma Y, Lu H, Tippin B et al. A biochemically defined system for mammalian nonhomologous DNA end joining. Mol Cell 2004; 16(5):701–713.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • Patrick C. Swanson
    • 1
  • Sushil Kumar
    • 1
  • Prafulla Raval
    • 1
  1. 1.Department of Medical Microbiology and ImmunologyCreighton University Medical CenterOmahaUSA

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