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Article

Base Flipping in V(D)J Recombination: Insights into the Mechanism of Hairpin Formation, the 12/23 Rule, and the Coordination of Double-Strand Breaks

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Pages 5889-5899 | Received 10 Feb 2009, Accepted 21 Aug 2009, Published online: 21 Mar 2023

REFERENCES

  • Agrawal, A., Q. M. Eastman, and D. G. Schatz. 1998. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 394:744–751.
  • Akamatsu, Y., and M. A. Oettinger. 1998. Distinct roles of RAG1 and RAG2 in binding the V(D)J recombination signal sequences. Mol. Cell. Biol. 18:4670–4678.
  • Ason, B., and W. S. Reznikoff. 2002. Mutational analysis of the base flipping event found in Tn5 transposition. J. Biol. Chem. 277:11284–11291.
  • Bassing, C. H., F. W. Alt, M. M. Hughes, M. D'Auteuil, T. D. Wehrly, B. B. Woodman, F. Gartner, J. M. White, L. Davidson, and B. P. Sleckman. 2000. Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule. Nature 405:583–586.
  • Bhasin, A., I. Y. Goryshin, and W. S. Reznikoff. 1999. Hairpin formation in Tn5 transposition. J. Biol. Chem. 274:37021–37029.
  • Bischerour, J., and R. Chalmers. 2009. Base flipping in Tn10 transposition: an active flip and capture mechanism. PLoS One 4:e6201.
  • Bischerour, J., and R. Chalmers. 2007. Base-flipping dynamics in a DNA hairpin processing reaction. Nucleic Acids Res. 35:2584–2595.
  • Bolland, S., and N. Kleckner. 1995. The two single-strand cleavages at each end of Tn10 occur in a specific order during transposition. Proc. Natl. Acad. Sci. USA 92:7814–7818.
  • Chalmers, R., A. Guhathakurta, H. Benjamin, and N. Kleckner. 1998. IHF modulation of Tn10 transposition: sensory transduction of supercoiling status via a proposed protein/DNA molecular spring. Cell 93:897–908.
  • Chalmers, R. M., and N. Kleckner. 1994. Tn10/IS10 transposase purification, activation, and in vitro reaction. J. Biol. Chem. 269:8029–8035.
  • Chou, S. H., K. H. Chin, and A. H. Wang. 2003. Unusual DNA duplex and hairpin motifs. Nucleic Acids Res. 31:2461–2474.
  • Ciubotaru, M., and D. G. Schatz. 2004. Synapsis of recombination signal sequences located in cis and DNA underwinding in V(D)J recombination. Mol. Cell. Biol. 24:8727–8744.
  • Claeys Bouuaert, C., and R. Chalmers. Gene therapy vectors: the prospects and potentials of the cut-and-paste transposons. Genetica, in press.
  • Coen, E. S., R. Carpenter, and C. Martin. 1986. Transposable elements generate novel spatial patterns of gene expression in Antirrhinum majus. Cell 47:285–296.
  • Crellin, P., and R. Chalmers. 2001. Protein-DNA contacts and conformational changes in the Tn10 transpososome during assembly and activation for cleavage. EMBO J. 20:3882–3891.
  • Crellin, P., S. Sewitz, and R. Chalmers. 2004. DNA looping and catalysis: the IHF-folded arm of Tn10 promotes conformational changes and hairpin resolution. Mol. Cell 13:537–547.
  • Cuomo, C. A., C. L. Mundy, and M. A. Oettinger. 1996. DNA sequence and structure requirements for cleavage of V(D)J recombination signal sequences. Mol. Cell. Biol. 16:5683–5690.
  • Curcio, M. J., and K. M. Derbyshire. 2003. The outs and ins of transposition: from mu to kangaroo. Nat. Rev. Mol. Cell Biol. 4:865–877.
  • Davies, D. R., I. Y. Goryshin, W. S. Reznikoff, and I. Rayment. 2000. Three-dimensional structure of the Tn5 synaptic complex transposition intermediate. Science 289:77–85.
  • Dawson, A., and D. J. Finnegan. 2003. Excision of the Drosophila mariner transposon mos1. Comparison with bacterial transposition and v(d)j recombination. Mol. Cell 11:225–235.
  • Drejer-Teel, A. H., S. D. Fugmann, and D. G. Schatz. 2007. The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Mol. Cell. Biol. 27:6288–6299.
  • Dyda, F., A. B. Hickman, T. M. Jenkins, A. Engelman, R. Craigie, and D. R. Davies. 1994. Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases. Science 266:1981–1986.
  • Early, P., H. Huang, M. Davis, K. Calame, and L. Hood. 1980. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell 19:981–992.
  • Eastman, Q. M., T. M. Leu, and D. G. Schatz. 1996. Initiation of V(D)J recombination in vitro obeying the 12/23 rule. Nature 380:85–88.
  • Eastman, Q. M., I. J. Villey, and D. G. Schatz. 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.
  • Fugmann, S. D., I. J. Villey, L. M. Ptaszek, and D. G. Schatz. 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.
  • Grundy, G. J., J. E. Hesse, and M. Gellert. 2007. Requirements for DNA hairpin formation by RAG1/2. Proc. Natl. Acad. Sci. USA 104:3078–3083.
  • Hickman, A. B., Z. N. Perez, L. Zhou, P. Musingarimi, R. Ghirlando, J. E. Hinshaw, N. L. Craig, and F. Dyda. 2005. Molecular architecture of a eukaryotic DNA transposase. Nat. Struct. Mol. Biol. 12:715–721.
  • Hiom, K., and M. Gellert. 1998. Assembly of a 12/23 paired signal complex: a critical control point in V(D)J recombination. Mol. Cell 1:1011–1019.
  • Hiom, K., M. Melek, and M. Gellert. 1998. DNA transposition by the RAG1 and RAG2 proteins: a possible source of oncogenic translocations. Cell 94:463–470.
  • Hughes, M. M., R. E. Tillman, T. D. Wehrly, J. M. White, and B. P. Sleckman. 2003. The B12/23 restriction is critically dependent on recombination signal nonamer and spacer sequences. J. Immunol. 171:6604–6610.
  • Jung, D., C. H. Bassing, S. D. Fugmann, H. L. Cheng, D. G. Schatz, and F. W. Alt. 2003. Extrachromosomal recombination substrates recapitulate beyond 12/23 restricted VDJ recombination in nonlymphoid cells. Immunity 18:65–74.
  • Kapitonov, V. V., and J. Jurka. 2005. RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS Biol. 3:e181.
  • Kennedy, A. K., A. Guhathakurta, N. Kleckner, and D. B. Haniford. 1998. Tn10 transposition via a DNA hairpin intermediate. Cell 95:125–134.
  • Kim, D. R., Y. Dai, C. L. Mundy, W. Yang, and M. A. Oettinger. 1999. Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase. Genes Dev. 13:3070–3080.
  • Kim, D. R., and M. A. Oettinger. 1998. Functional analysis of coordinated cleavage in V(D)J recombination. Mol. Cell. Biol. 18:4679–4688.
  • Klenchin, V. A., A. Czyz, I. Y. Goryshin, R. Gradman, S. Lovell, I. Rayment, and W. S. Reznikoff. 2008. Phosphate coordination and movement of DNA in the Tn5 synaptic complex: role of the (R)YREK motif. Nucleic Acids Res. 36:5855–5862.
  • Koralov, S. B., T. I. Novobrantseva, K. Hochedlinger, R. Jaenisch, and K. Rajewsky. 2005. Direct in vivo VH to JH rearrangement violating the 12/23 rule. J. Exp. Med. 201:341–348.
  • Landree, M. A., J. A. Wibbenmeyer, and D. B. Roth. 1999. 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. 13:3059–3069.
  • Lee, G. S., M. B. Neiditch, S. S. Salus, and D. B. Roth. 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.
  • Liu, D., J. Bischerour, A. Siddique, N. Buisine, Y. Bigot, and R. Chalmers. 2007. The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase. Mol. Cell. Biol. 27:1125–1132.
  • Liu, D., P. Crellin, and R. Chalmers. 2005. Cyclic changes in the affinity of protein-DNA interactions drive the progression and regulate the outcome of the Tn10 transposition reaction. Nucleic Acids Res. 33:1982–1992.
  • Liu, D., S. Sewitz, P. Crellin, and R. Chalmers. 2006. Functional coupling between the two active sites during Tn 10 transposition buffers the mutation of sequences critical for DNA hairpin processing. Mol. Microbiol. 62:1522–1533.
  • Lu, C. P., J. E. Posey, and D. B. Roth. 2008. Understanding how the V(D)J recombinase catalyzes transesterification: distinctions between DNA cleavage and transposition. Nucleic Acids Res. 36:2864–2873.
  • Lu, C. P., H. Sandoval, V. L. Brandt, P. A. Rice, and D. B. Roth. 2006. Amino acid residues in Rag1 crucial for DNA hairpin formation. Nat. Struct. Mol. Biol. 13:1010–1015.
  • McBlane, J. F., D. C. van Gent, D. A. Ramsden, C. Romeo, C. A. Cuomo, M. Gellert, and M. A. Oettinger. 1995. Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps. Cell 83:387–395.
  • Mitra, R., J. Fain-Thornton, and N. L. Craig. 2008. piggyBac can bypass DNA synthesis during cut and paste transposition. EMBO J. 27:1097–1109.
  • Munoz-Lopez, M., A. Siddique, J. Bischerour, P. Lorite, R. Chalmers, and T. Palomeque. 2008. Transposition of Mboumar-9: identification of a new naturally active mariner-family transposon. J. Mol. Biol. 382:567–572.
  • Nakajima, P. B., and M. J. Bosma. 1997. Characterization of excised DNA intermediates associated with V(D)J recombination at the T-cell receptor δ locus. Mol. Cell. Biol. 17:2631–2641.
  • Nishihara, T., F. Nagawa, T. Imai, and H. Sakano. 2008. RAG-heptamer interaction in the synaptic complex is a crucial biochemical checkpoint for the 12/23 recombination rule. J. Biol. Chem. 283:4877–4885.
  • Nowotny, M., S. A. Gaidamakov, R. J. Crouch, and W. Yang. 2005. Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis. Cell 121:1005–1016.
  • Park, H., K. Zhang, Y. Ren, S. Nadji, N. Sinha, J. S. Taylor, and C. Kang. 2002. Crystal structure of a DNA decamer containing a cis-syn thymine dimer. Proc. Natl. Acad. Sci. USA 99:15965–15970.
  • Ramsden, D. A., and M. Gellert. 1995. Formation and resolution of double-strand break intermediates in V(D)J rearrangement. Genes Dev. 9:2409–2420.
  • Ramsden, D. A., J. F. McBlane, D. C. van Gent, and M. Gellert. 1996. Distinct DNA sequence and structure requirements for the two steps of V(D)J recombination signal cleavage. EMBO J. 15:3197–3206.
  • Rice, P., R. Craigie, and D. R. Davies. 1996. Retroviral integrases and their cousins. Curr. Opin. Struct. Biol. 6:76–83.
  • Roberts, R. J., and X. Cheng. 1998. Base flipping. Annu. Rev. Biochem. 67:181–198.
  • Roth, D. B., J. P. Menetski, P. B. Nakajima, M. J. Bosma, and M. Gellert. 1992. V(D)J recombination: broken DNA molecules with covalently sealed (hairpin) coding ends in scid mouse thymocytes. Cell 70:983–991.
  • Santagata, S., V. Aidinis, and E. Spanopoulou. 1998. The effect of Me2+ cofactors at the initial stages of V(D)J recombination. J. Biol. Chem. 273:16325–16331.
  • Santagata, S., E. Besmer, A. Villa, F. Bozzi, J. S. Allingham, C. Sobacchi, D. B. Haniford, P. Vezzoni, M. C. Nussenzweig, Z. Q. Pan, and P. Cortes. 1999. The RAG1/RAG2 complex constitutes a 3′ flap endonuclease: implications for junctional diversity in V(D)J and transpositional recombination. Mol. Cell 4:935–947.
  • Sawchuk, D. J., F. Weis-Garcia, S. Malik, E. Besmer, M. Bustin, M. C. Nussenzweig, and P. Cortes. 1997. 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. 185:2025–2032.
  • Sewitz, S., P. Crellin, and R. Chalmers. 2003. The positive and negative regulation of Tn10 transposition by IHF is mediated by structurally asymmetric transposon arms. Nucleic Acids Res. 31:5868–5876.
  • Slupphaug, G., C. D. Mol, B. Kavli, A. S. Arvai, H. E. Krokan, and J. A. Tainer. 1996. A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature 384:87–92.
  • Steen, S. B., L. Gomelsky, S. L. Speidel, and D. B. Roth. 1997. Initiation of V(D)J recombination in vivo: role of recombination signal sequences in formation of single and paired double-strand breaks. EMBO J. 16:2656–2664.
  • Stivers, J. T. 2008. Extrahelical damaged base recognition by DNA glycosylase enzymes. Chemistry 14:786–793.
  • Stivers, J. T. 2004. Site-specific DNA damage recognition by enzyme-induced base flipping. Prog. Nucleic Acid Res. Mol. Biol. 77:37–65.
  • Swanson, P. C. 2002. A RAG-1/RAG-2 tetramer supports 12/23-regulated synapsis, cleavage, and transposition of V(D)J recombination signals. Mol. Cell. Biol. 22:7790–7801.
  • Swanson, P. C. 2002. Fine structure and activity of discrete RAG-HMG complexes on V(D)J recombination signals. Mol. Cell. Biol. 22:1340–1351.
  • Swanson, P. C. 2004. The bounty of RAGs: recombination signal complexes and reaction outcomes. Immunol. Rev. 200:90–114.
  • Swanson, P. C. 2001. 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. 21:449–458.
  • van Dongen, M. J., M. M. Mooren, E. F. Willems, G. A. van der Marel, J. H. van Boom, S. S. Wijmenga, and C. W. Hilbers. 1997. Structural features of the DNA hairpin d(ATCCTA-GTTA-TAGGAT): formation of a G-A base pair in the loop. Nucleic Acids Res. 25:1537–1547.
  • van Gent, D. C., J. F. McBlane, D. A. Ramsden, M. J. Sadofsky, J. E. Hesse, and M. Gellert. 1995. Initiation of V(D)J recombination in a cell-free system. Cell 81:925–934.
  • van Gent, D. C., D. A. Ramsden, and M. Gellert. 1996. The RAG1 and RAG2 proteins establish the 12/23 rule in V(D)J recombination. Cell 85:107–113.
  • West, R. B., and M. R. Lieber. 1998. The RAG-HMG1 complex enforces the 12/23 rule of V(D)J recombination specifically at the double-hairpin formation step. Mol. Cell. Biol. 18:6408–6415.
  • Wong, S. Y., C. P. Lu, and D. B. Roth. 2008. A RAG1 mutation found in Omenn syndrome causes coding flank hypersensitivity: a novel mechanism for antigen receptor repertoire restriction. J. Immunol. 181:4124–4130.
  • Yang, W., J. Y. Lee, and M. Nowontny. 2006. Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity. Mol. Cell 22:5–13.
  • Yu, K., and M. R. Lieber. 2000. The nicking step in V(D)J recombination is independent of synapsis: implications for the immune repertoire. Mol. Cell. Biol. 20:7914–7921.
  • Zhou, L., R. Mitra, P. W. Atkinson, A. B. Hickman, F. Dyda, and N. L. Craig. 2004. Transposition of hAT elements links transposable elements and V(D)J recombination. Nature 432:995–1001.

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