Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination

Landree, M. A.; Wibbenmeyer, J. A.; Roth, D. B.

doi:10.1101/gad.13.23.3059

PreprintCited by 209DNA Repair MechanismsCRISPR and Genetic EngineeringT-cell and B-cell Immunology

Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination

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Landree, M. A., Wibbenmeyer, J. A., Roth, D. B.·1999·Genes & Development

DOI 10.1101/gad.13.23.3059PMC PMC317185

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Abstract

RAG1 and RAG2 initiate V(D)J recombination, the process of rearranging the antigen-binding domain of immunoglobulins and T-cell receptors, by introducing site-specific double-strand breaks (DSB) in chromosomal DNA during lymphocyte development. These breaks are generated in two steps, nicking of one strand (hydrolysis), followed by hairpin formation (transesterification). The nature and location of the RAG active site(s) have remained unknown. Because acidic amino acids have a critical role in catalyzing DNA cleavage by nucleases and recombinases that require divalent metal ions as cofactors, we hypothesized that acidic active site residues are likewise essential for RAG-mediated DNA cleavage. We altered each conserved acidic amino acid in RAG1 and RAG2 by site-directed mutagenesis, and examined >100 mutants using a combination of in vivo and in vitro analyses. No conserved acidic amino acids in RAG2 were critical for catalysis; three RAG1 mutants retained normal DNA binding, but were catalytically inactive for both nicking and hairpin formation. These data argue that one active site in RAG1 performs both steps of the cleavage reaction. Amino acid substitution experiments that changed the metal ion specificity suggest that at least one of these three residues contacts the metal ion(s) directly. These data suggest that RAG-mediated DNA cleavage involves coordination of divalent metal ion(s) by RAG1.

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All three core residues from the catalytic DDE triad in RAG1 proteins (residues 603, 711, and 965) necessary for V(D)J recombination are conserved in Transib TPases.
“All three core residues from the catalytic DDE triad in the RAG1 proteins (residues 603, 711, and 965) that are necessary for V(D)J recombination [21,22] are conserved in the Transib TPases (Figures 3 and Figure S3).”
From RAG1 Core and V(D)J Recombination Signal Sequences Were Derived from Transib Transposons (2005) · cites this paper as [22]

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[19] Rapid and efficient site-specific mutagenesis without phenotypic selection
Kunkel, T. A., Roberts, J. D., & Zakour, R. A. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(87)54085-x · Cited by 5,341 · see citing works
Selective extraction of polyoma DNA from infected mouse cell cultures
Hirt, B. (1967) · Journal of Molecular Biology · doi:10.1016/0022-2836(67)90307-5 · Cited by 5,294 · see citing works
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system
Agrawal, A., Eastman, Q. M., & Schatz, D. G. (1998) · Nature · doi:10.1038/29457 · Cited by 811 · see citing works
Cleavage at a V(D)J recombination signal requires only RAG1 and RAG2 proteins and occurs in two steps
McBlane, J. F., van Gent, D. C., Ramsden, D. A., Romeo, C., Cuomo, C. A., Gellert, M. F., & Oettinger, M. A. (1995) · Cell · doi:10.1016/0092-8674(95)90116-7 · Cited by 706 · see citing works
HIV-1 DNA integration: Mechanism of viral DNA cleavage and DNA strand transfer
Engelman, A., Mizuuchi, K., & Craigie, R. (1991) · Cell · doi:10.1016/0092-8674(91)90297-c · Cited by 655 · see citing works
Residues Critical for Retroviral Integrative Recombination in a Region That Is Highly Conserved among Retroviral/Retrotransposon Integrases and Bacterial Insertion Sequence Transposases
Kulkosky, J., Jones, K. S., Katz, R. A., Mack, J. P. G., & Skalka, A. M. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.5.2331 · Cited by 567 · see citing works
DNA Transposition by the RAG1 and RAG2 Proteins
Hiom, K., Melek, M., & Gellert, M. (1998) · Cell · doi:10.1016/s0092-8674(00)81587-1 · Cited by 534 · see citing works
Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro
Engelman, A., & Craigie, R. (1992) · Journal of Virology · doi:10.1128/jvi.66.11.6361-6369.1992 · Cited by 519 · see citing works
V(D)J recombination: Broken DNA molecules with covalently sealed (hairpin) coding ends in scid mouse thymocytes
Roth, D. B., Menetski, J. P., Nakajima, P. B., Bosma, M. J., & Gellert, M. F. (1992) · Cell · doi:10.1016/0092-8674(92)90248-b · Cited by 440 · see citing works
Self-citation
Metal ion catalysis in the Tetrahymena ribozyme reaction
Piccirilli, J. A., Vyle, J. S., Caruthers, M. H., & Cech, T. R. (1993) · Nature · doi:10.1038/361085a0 · Cited by 386 · see citing works
Three new structures of the core domain of HIV-1 integrase: An active site that binds magnesium
Goldgur, Y., Dyda, F., Hickman, A. B., Jenkins, T. M., Craigie, R., & Davies, D. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9150 · Cited by 380 · see citing works
Reversal of Integration and DNA Splicing Mediated by Integrase of Human Immunodeficiency Virus
Chow, S. A., Vincent, K. A., Ellison, V., & Brown, P. O. (1992) · Science · doi:10.1126/science.1738845 · Cited by 379 · see citing works
Role of divalent metal ions in the hammerhead RNA cleavage reaction
Dahm, S. C., & Uhlenbeck, O. C. (1991) · Biochemistry · doi:10.1021/bi00103a011 · Cited by 367 · see citing works
The RAG1 and RAG2 Proteins Establish the 12/23 Rule in V(D)J Recombination
van Gent, D. C., Ramsden, D. A., & Gellert, M. F. (1996) · Cell · doi:10.1016/s0092-8674(00)81086-7 · Cited by 287 · see citing works
Initiation of V(D)J recombination in a cell-free system
van Gent, D. C., McBlane, J. F., Ramsden, D. A., Sadofsky, M. J., Hesse, J. E., & Gellert, M. F. (1995) · Cell · doi:10.1016/0092-8674(95)90012-8 · Cited by 284 · see citing works
ACCESSIBILITY CONTROL OF ANTIGEN-RECEPTOR VARIABLE-REGION GENE ASSEMBLY: Role ofcis-Acting Elements
Sleckman, B. P., Gorman, J. R., & Alt, F. W. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.459 · Cited by 284 · see citing works
Similarities Between Initiation of V(D)J Recombination and Retroviral Integration
van Gent, D. C., Mizuuchi, K., & Gellert, M. F. (1996) · Science · doi:10.1126/science.271.5255.1592 · Cited by 283 · see citing works
Crystal structures of the catalytic domain of HIV-1 integrase free and complexed with its metal cofactor: high level of similarity of the active site with other viral integrases 1 1Edited by R. Huber
Maignan, S., Guilloteau, J. P., Zhou, Q., Clément-Mella, C., & Mikol, V. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2002 · Cited by 277 · see citing works
Chromosomal Translocations In Lymphoid Malignancies Reveal Novel Proto-Oncogenes
Korsmeyer, S. J. (1992) · Annual Review of Immunology · doi:10.1146/annurev.iy.10.040192.004033 · Cited by 256 · see citing works
Residues Critical for Retroviral Integrative Recombination in a Region That Is Highly Conserved among Retroviral/Retrotransposon Integrases and Bacterial Insertion Sequence Transposases
Kulkosky, J., Jones, K. S., Katz, R. A., et al. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.5.2331-2338.1992 · Cited by 246 · see citing works
High-resolution Structure of the Catalytic Domain of Avian Sarcoma Virus Integrase
Bujacz, G., Jaskólski, M., Alexandratos, J. N., Wlodawer, A., Merkel, G. W., Katz, R. A., & Skalka, A. M. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0556 · Cited by 226 · see citing works
The Homeodomain Region of Rag-1 Reveals the Parallel Mechanisms of Bacterial and V(D)J Recombination
Spanopoulou, E., Zaitseva, F., Wang, F.-H., Santagata, S., Baltimore, D., & Panayotou, G. (1996) · Cell · doi:10.1016/s0092-8674(00)81344-6 · Cited by 225 · see citing works
Structure of the bacteriophage Mu transposase core: A common structural motif for DNA transposition and retroviral integration
Rice, P. A., & Mizuuchi, K. (1995) · Cell · doi:10.1016/0092-8674(95)90308-9 · Cited by 222 · see citing works
A Stable RAG1–RAG2–DNA Complex That Is Active in V(D)J Cleavage
Hiom, K. J., & Gellert, M. F. (1997) · Cell · doi:10.1016/s0092-8674(00)81859-0 · Cited by 207 · see citing works
Bacterial transposases and retroviral integrases
Polard, P., & Chandler, M. (1995) · Molecular Microbiology · doi:10.1111/j.1365-2958.1995.tb02217.x · Cited by 206 · see citing works
RAG1 Mediates Signal Sequence Recognition and Recruitment of RAG2 in V(D)J Recombination
Difilippantonio, M. J., McMahan, C. J., Eastman, Q., Spanopoulou, E., & Schatz, D. G. (1996) · Cell · doi:10.1016/s0092-8674(00)81343-4 · Cited by 203 · see citing works
Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase
Kim, D. R., Dai, Y., Mundy, C. L., Yang, W., & Oettinger, M. A. (1999) · Genes & Development · doi:10.1101/gad.13.23.3070 · Cited by 199 · see citing works
Tn10 Transposition via a DNA Hairpin Intermediate
Kennedy, A. K., Guhathakurta, A., Kleckner, N. E., & Haniford, D. B. (1998) · Cell · doi:10.1016/s0092-8674(00)81788-2 · Cited by 199 · see citing works
Expression and V(D)J recombination activity of mutated RAG-1 proteins
Sadofsky, M. J., Hesse, J. E., McBlane, J. F., & Gellert, M. F. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.3.550 · Cited by 193 · see citing works
The catalytic domain of avian sarcoma virus integrase: conformation of the active-site residues in the presence of divalent cations
Bujacz, G., Jaskólski, M., Alexandratos, J. N., Wlodawer, A., Merkel, G., Katz, R. A., & Skalka, A. M. (1996) · Structure · doi:10.1016/s0969-2126(96)00012-3 · Cited by 170 · see citing works
Expression and V(D)J recombination activity of mutated RAG-1 proteins
Sadofsky, M. J., Hessw, J. E., McBlane, J. F., & Gellert, M. F. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.24.5644 · Cited by 168 · see citing works
Inversion of the phosphate chirality at the target site of Mu DNA strand transfer: Evidence for a one-step transesterification mechanism
Mizuuchi, K., & Adzuma, K. (1991) · Cell · doi:10.1016/0092-8674(91)90145-o · Cited by 165 · see citing works
Characterization of broken DNA molecules associated with V(D)J recombination.
Roth, D. B., Zhu, C., & Gellert, M. F. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10788 · Cited by 161 · see citing works
Self-citation
Dispensable sequence motifs in the RAG-1 and RAG-2 genes for plasmid V(D)J recombination.
Silver, D. P., Spanopoulou, E., Mulligan, R. C., & Baltimore, D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.13.6100 · Cited by 160 · see citing works
The Tn7 transposase is a heteromeric complex in which DNA breakage and joining activities are distributed between different gene products.
Sarnovsky, R. J., May, E. W., & Craig, N. L. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01024.x · Cited by 160 · see citing works
Definition of a core region of RAG-2 that is functional in V(D)J recombination
Sadofsky, M. J., Hesse, J. E., & Gellert, M. F. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.10.1805 · Cited by 156 · see citing works
Chromosomal translocations in lymphoid neoplasia: a reappraisal of the recombinase model.
Tycko, B., & Sklar, J. L. (1990) · PubMed · Cited by 140 · see citing works
Identification of residues in the Mu transposase essential for catalysis.
Baker, T. A., & Luo, L. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.14.6654 · Cited by 138 · see citing works
Distinct Roles of RAG1 and RAG2 in Binding the V(D)J Recombination Signal Sequences
Akamatsu, Y., & Oettinger, M. A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.8.4670 · Cited by 136 · see citing works
Analysis of regions of RAG-2 important for V(D)J recombination
Cuomo, C. A., & Oettinger, M. A. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.10.1810 · Cited by 132 · see citing works
Hairpin Coding End Opening Is Mediated by RAG1 and RAG2 Proteins
Besmer, E., Mansilla‐Soto, J., Cassard, S., Sawchuk, D. J., Brown, G., Sadofsky, M. J., Lewis, S. M., Nussenzweig, M. C., & Cortés, P. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80296-8 · Cited by 130 · see citing works
Site-specific hydrolysis and alcoholysis of human immunodeficiency virus DNa termini mediated by the viral integrase protein
Vink, C., Yeheskiely, E., van der MAREL, G. A., BOOM, J. H. V., & Plasterk, R. H. A. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.24.6691 · Cited by 129 · see citing works
DNA Hairpin Opening Mediated by the RAG1 and RAG2 Proteins
Shockett, P. E., & Schatz, D. G. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4159 · Cited by 117 · see citing works
VDJ Recombination
Roth, D. B., & Craig, N. L. (1998) · Cell · doi:10.1016/s0092-8674(00)81580-9 · Cited by 115 · see citing works
Self-citation
V(D)J Recombination Signal Recognition
Swanson, P. C., & Desiderio, S. V. (1998) · Immunity · doi:10.1016/s1074-7613(00)80593-2 · Cited by 115 · see citing works
Rejoining of DNA by the RAG1 and RAG2 Proteins
Melek, M., Gellert, M. F., & van Gent, D. C. (1998) · Science · doi:10.1126/science.280.5361.301 · Cited by 108 · see citing works
The Three Chemical Steps of Tn10/IS10 Transposition Involve Repeated Utilization of a Single Active Site
Bolland, S. M., & Kleckner, N. E. (1996) · Cell · doi:10.1016/s0092-8674(00)80977-0 · Cited by 106 · see citing works
Avoiding self: two Tn7‐encoded proteins mediate target immunity in Tn7 transposition
Stellwagen, A. E., & Craig, N. L. (1997) · The EMBO Journal · doi:10.1093/emboj/16.22.6823 · Cited by 105 · see citing works
Polynucleotidyl transfer reactions in site‐specific DNA recombination
Mizuuchi, K. (1997) · Genes to Cells · doi:10.1046/j.1365-2443.1997.970297.x · Cited by 100 · see citing works
RAG-2 Promotes Heptamer Occupancy by RAG-1 in the Assembly of a V(D)J Initiation Complex
Swanson, P. C., & Desiderio, S. V. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3674 · Cited by 98 · see citing works
The 12/23 rule is enforced at the cleavage step of V(D)J recombination in vivo
Steen, S. B., Gomelsky, L., & Roth, D. B. (1996) · Genes to Cells · doi:10.1046/j.1365-2443.1996.d01-259.x · Cited by 81 · see citing works
Self-citation
EcoRV restriction endonuclease: communication between catalytic metal ions and DNA recognition
Vermote, C. L. M., & Halford, S. E. (1992) · Biochemistry · doi:10.1021/bi00141a018 · Cited by 79 · see citing works
DNA transposition: From a black box to a color monitor
Grindley, N. D. F., & Leschziner, A. E. (1995) · Cell · doi:10.1016/0092-8674(95)90132-9 · Cited by 74 · see citing works
Detection of RAG Protein-V(D)J Recombination Signal Interactions Near the Site of DNA Cleavage by UV Cross-Linking
Eastman, Q., Villey, I. J., & Schatz, D. G. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3788 · Cited by 71 · see citing works
A RAG1 and RAG2 Tetramer Complex Is Active in Cleavage in V(D)J Recombination
Tu, B., Mo, X., & Sadofsky, M. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.7.4664 · Cited by 71 · see citing works
The same two monomers within a MuA tetramer provide the DDE domains for the strand cleavage and strand transfer steps of transposition
Namgoong, S. Y., & Harshey, R. M. (1998) · The EMBO Journal · doi:10.1093/emboj/17.13.3775 · Cited by 70 · see citing works
RAG-1 mutations that affect the target specificity of V(D)j recombination: a possible direct role of RAG-1 in site recognition.Preprint
Sadofsky, M. J., Hesse, J. E., van Gent, D. C., & Gellert, M. F. (1995) · Genes & Development · doi:10.1101/gad.9.17.2193 · Cited by 69 · see citing works
Footprint Analysis of the RAG Protein Recombination Signal Sequence Complex for V(D)J Type Recombination
Nagawa, F., Ishiguro, K., Tsuboi, A., Yoshida, T., Ishikawa, A., Takemori, T., Otsuka, A. J., & Sakano, H. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.1.655 · Cited by 69 · see citing works
Step-arrest Mutants of Phage Mu Transposase
Kim, K., Namgoong, S. Y., Jayaram, M., & Harshey, R. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.1472 · Cited by 67 · see citing works
Organization and dynamics of the Mu transpososome: recombination by communication between two active sitesPreprint
Williams, T., Jackson, E. L., Carritte, A., & Baker, T. A. (1999) · Genes & Development · doi:10.1101/gad.13.20.2725 · Cited by 67 · see citing works
Functional Analysis of Coordinated Cleavage in V(D)J Recombination
Kim, D. R., & Oettinger, M. A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.8.4679 · Cited by 66 · see citing works
A dimer of the lymphoid protein RAG1 recognizes the recombination signal sequence and the complex stably incorporates the high mobility group protein HMG2
Rodgers, K. K. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.14.2938 · Cited by 65 · see citing works
Initiation of V(D)J recombination in vivo: role of recombination signal sequences in formation of single and paired double‐strand breaks
Steen, S. B., Gomelsky, L., Speidel, S. L., & Roth, D. B. (1997) · The EMBO Journal · doi:10.1093/emboj/16.10.2656 · Cited by 62 · see citing works
Self-citation
Ku86 Is Not Required for Protection of Signal Ends or for Formation of Nonstandard V(D)J Recombination Products
Han, J.-O., Steen, S. B., & Roth, D. B. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.4.2226 · Cited by 61 · see citing works
Self-citation
Regions of RAG1 protein critical for V(D)J recombination
Kirch, S. A., Sudarsanam, P., & Oettinger, M. A. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260425 · Cited by 60 · see citing works
All three residues of the Tn 10 transposase DDE catalytic triad function in divalent metal ion binding 1 1Edited by M. Gottesman
Allingham, J. S., Pribil, P. A., & Haniford, D. B. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2837 · Cited by 54 · see citing works
DNA substrate requirements for different activities of the human immunodeficiency virus type 1 integrase protein
van den Ent, F. M. I., Vink, C., & Plasterk, R. H. A. (1994) · Journal of Virology · doi:10.1128/jvi.68.12.7825-7832.1994 · Cited by 51 · see citing works
Intermolecular disintegration and intramolecular strand transfer activities of wild-type and mutant HIV-1 integrase
Mazumder, A., Engelman, A., Craigie, R., Fesen, M. R., & Pommier, Y. G. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.6.1037 · Cited by 50 · see citing works
Wild‐type Flp recombinase cleaves DNA in trans
Lee, J., Jayaram, M., & Grainge, I. (1999) · The EMBO Journal · doi:10.1093/emboj/18.3.784 · Cited by 46 · see citing works
Structure–function correlation for the EcoRV restriction enzyme: from non‐specific binding to specific DNA cleavage
Vipond, I. B., & Halford, S. E. (1993) · Molecular Microbiology · doi:10.1111/j.1365-2958.1993.tb01685.x · Cited by 34 · see citing works
UPDATE: V(D)J Recombination and Transposition: Closer Than Expected
Craig, N. L. (1996) · Science · doi:10.1126/science.271.5255.1512 · Cited by 29 · see citing works
Intermolecular V(D)J Recombination Is Prohibited Specifically at the Joining Step
Han, J.-O., Steen, S. B., & Roth, D. B. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80460-8 · Cited by 29 · see citing works
Self-citation
Mutational Analysis of the Mu Transposase
Krementsova, E. B., Giffin, M. J., Pincus, D., & Baker, T. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.47.31358 · Cited by 29 · see citing works
Differential Effects of Moloney Murine Leukemia Virus Reverse Transcriptase Mutations on RNase H Activity in Mg2+ and Mn2+
Blain, S. W., & Goff, S. P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.3.1448 · Cited by 20 · see citing works

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Bassing, C. H., Swat, W., & Alt, F. W. (2002) · Cell · doi:10.1016/s0092-8674(02)00675-x · Cited by 968 · see citing works
V(D)J Recombination: RAG Proteins, Repair Factors, and Regulation
Gellert, M. F. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.090501.150203 · Cited by 752 · see citing works
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Yang, W. (2011) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583510000181 · Cited by 692 · see citing works
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Kapitonov, V. V., & Jurka, J. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030181 · Cited by 521 · see citing works
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Davies, D. R., Goryshin, I. Y., Reznikoff, W. S., & Rayment, I. (2000) · Science · doi:10.1126/science.289.5476.77 · Cited by 427 · see citing works
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Li, L., Olvera, J. M., Yoder, K., Mitchell, R., Butler, S., Lieber, M., Martin, S. L., & Bushman, F. D. (2001) · EMBO Journal · doi:10.1093/emboj/20.12.3272 · Cited by 386 · see citing works
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Corneo, B., Wendland, R. L., Deriano, L., Cui, X., Klein, I. A., Wong, S.-Y., Arnal, S. M., Holub, A. J., Weller, G. R., Pancake, B. A., et al. (2007) · Nature · doi:10.1038/nature06168 · Cited by 331 · see citing works
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Self-citation
Human RAG mutations: biochemistry and clinical implications
Notarangelo, L. D., Kim, M., Walter, J. E., & Lee, Y. N. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.28 · Cited by 232 · see citing works
Transposition of hAT elements links transposable elements and V(D)J recombination
Zhou, L., Mitra, R., Atkinson, P. W., Burgess Hickman, A., Dyda, F., & Craig, N. L. (2004) · Nature · doi:10.1038/nature03157 · Cited by 224 · see citing works
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
Corneo, B., Moshous, D., Güngör, T., Wulffraat, N. M., Philippet, P., Deist, F. L., Fischer, A., & de Villartay, J. (2001) · Blood · doi:10.1182/blood.v97.9.2772 · Cited by 213 · see citing works
Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase
Kim, D. R., Dai, Y., Mundy, C. L., Yang, W., & Oettinger, M. A. (1999) · Genes & Development · doi:10.1101/gad.13.23.3070 · Cited by 199 · see citing works
Retroviral integrase superfamily: the structural perspective
Nowotny, M. (2009) · The EMBO Reports · doi:10.1038/embor.2008.256 · Cited by 183 · see citing works
An ancient evolutionary origin of the <i>Rag1</i> / <i>2</i> gene locus
Fugmann, S. D., Messier, C., Novack, L. A., Cameron, R. A., & Rast, J. P. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509720103 · Cited by 177 · see citing works
Crystal structure of the V(D)J recombinase RAG1–RAG2
Kim, M.-S., Lapkouski, M., Yang, W., & Gellert, M. F. (2015) · Nature · doi:10.1038/nature14174 · Cited by 172 · see citing works
The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells
Karo, J. M., Schatz, D. G., & Sun, J. C.-Y. (2014) · Cell · doi:10.1016/j.cell.2014.08.026 · Cited by 168 · see citing works
Identification of Two Catalytic Residues in RAG1 that Define a Single Active Site within the RAG1/RAG2 Protein Complex
Fugmann, S. D., Villey, I. J., Ptaszek, L. M., & Schatz, D. G. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80406-2 · Cited by 165 · see citing works
RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci
Hewitt, S. L., Yin, B., Ji, Y., Chaumeil, J., Marszalek, K., Tenthorey, J. L., Salvagiotto, G., Steinel, N. C., Ramsey, L. B., Ghysdael, J., et al. (2009) · Nature Immunology · doi:10.1038/ni.1735 · Cited by 151 · see citing works
The “Dispensable” Portion of RAG2 Is Necessary for Efficient V-to-DJ Rearrangement during B and T Cell Development
Liang, H.-E., Hsu, L., Cado, D., Cowell, L. G., Kelsoe, G. H., & Schlissel, M. S. (2002) · Immunity · doi:10.1016/s1074-7613(02)00448-x · Cited by 153 · see citing works
Integrating prokaryotes and eukaryotes: DNA transposases in light of structure
Hickman, A. B., Chandler, M., & Dyda, F. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409230903505596 · Cited by 151 · see citing works
Tn5 as a model for understanding DNA transposition
Reznikoff, W. S. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03382.x · Cited by 138 · see citing works
RAG-dependent primary immunodeficiencies
Sobacchi, C., Marrella, V., Rucci, F., Vezzoni, P., & VILLA, A. M. (2006) · Human Mutation · doi:10.1002/humu.20408 · Cited by 136 · see citing works
Molecular architecture of a eukaryotic DNA transposase
Hickman, A. B., Perez, Z. N., Zhou, L., Musingarimi, P., Ghirlando, R., Hinshaw, J. E., Craig, N. L., & Dyda, F. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb970 · Cited by 130 · see citing works
Roles for NBS1 in Alternative Nonhomologous End-Joining of V(D)J Recombination Intermediates
Deriano, L., Stracker, T. H., Baker, A. M., Petrini, J. H. J., & Roth, D. B. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.03.009 · Cited by 123 · see citing works
Self-citation
The bounty of RAGs: recombination signal complexes and reaction outcomes
Swanson, P. C. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00159.x · Cited by 119 · see citing works
Biochemical, Structural, and Physiological Characterization of Terminal Deoxynucleotidyl Transferase
Fowler, J. D., & Suo, Z. (2006) · Chemical Reviews · doi:10.1021/cr040445w · Cited by 119 · see citing works
The taming of a transposon: V(D)J recombination and the immune system
Jones, J. M., & Gellert, M. F. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00168.x · Cited by 112 · see citing works
New insights into the evolutionary origins of the recombination‐activating gene proteins and V(D)J recombination
Carmona, L. M., & Schatz, D. G. (2016) · FEBS Journal · doi:10.1111/febs.13990 · Cited by 113 · see citing works
The origins of the Rag genes—From transposition to V(D)J recombination
Fugmann, S. D. (2009) · Seminars in Immunology · doi:10.1016/j.smim.2009.11.004 · Cited by 112 · see citing works
ThehATand CACTA Superfamilies of Plant Transposons
Kunze, R., & Weil, C. F. (2007) · Wiley eBooks · doi:10.1128/9781555817954.ch24 · Cited by 110 · see citing works
Ordered assembly of the V(D)J synaptic complex ensures accurate recombination
Jones, J. M., & Gellert, M. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf394 · Cited by 105 · see citing works
The RAG proteins in V(D)J recombination: more than just a nuclease
Sadofsky, M. J. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.7.1399 · Cited by 103 · see citing works
Separation-of-Function Mutants Reveal Critical Roles for RAG2 in Both the Cleavage and Joining Steps of V(D)J Recombination
Qiu, J.-X., Kale, S. B., Schultz, H. Y., & Roth, D. B. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00156-3 · Cited by 97 · see citing works
Self-citation
Regulation and Evolution of the RAG Recombinase
Teng, G., & Schatz, D. G. (2015) · Advances in immunology · doi:10.1016/bs.ai.2015.07.002 · Cited by 92 · see citing works
Retroviral Integrase Structure and DNA Recombination Mechanism
Engelman, A., & Cherepanov, P. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.mdna3-0024-2014 · Cited by 95 · see citing works
Role of recombination activating genes in the generation of antigen receptor diversity and beyond
Nishana, M., & Raghavan, S. C. (2012) · Immunology · doi:10.1111/imm.12009 · Cited by 95 · see citing works
Genomic DNA transposition induced by human PGBD5
Henssen, A. G., Hénaff, E. M., Jiang, E., Eisenberg, A., Carson, J., Villasante, C. M., Ray, M., Still, E., Burns, M., Gandara, J. A., et al. (2015) · eLife · doi:10.7554/elife.10565 · Cited by 94 · see citing works
Chromatin Topology and the Regulation of Antigen Receptor Assembly
Bossen, C., Månsson, R., & Murre, C. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075003 · Cited by 92 · see citing works
Human PGBD5 DNA transposase promotes site-specific oncogenic mutations in rhabdoid tumors
Henssen, A. G., Koche, R. P., Zhuang, J., Jiang, E., Reed, C., Eisenberg, A., Still, E., MacArthur, I. C., Rodríguez-Fos, E., González, S., et al. (2017) · Nature Genetics · doi:10.1038/ng.3866 · Cited by 88 · see citing works
Cracking the DNA Code for V(D)J Recombination
Kim, M., Chuenchor, W., Chen, X., Cui, Y., Zhang, X., Zhou, Z., Gellert, M. F., & Yang, W. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.03.008 · Cited by 89 · see citing works
DNA damage: a trigger of innate immunity but a requirement for adaptive immune homeostasis
Xu, Y. (2006) · Nature reviews. Immunology · doi:10.1038/nri1804 · Cited by 86 · see citing works
A RAG-1/RAG-2 Tetramer Supports 12/23-Regulated Synapsis, Cleavage, and Transposition of V(D)J Recombination Signals
Swanson, P. C. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.22.7790-7801.2002 · Cited by 82 · see citing works
Long-Range Regulation of V(D)J Recombination
Proudhon, C., Hao, B., Raviram, R., Chaumeil, J., & Skok, J. A. (2015) · Advances in immunology · doi:10.1016/bs.ai.2015.07.003 · Cited by 77 · see citing works
Antigen receptor genes and the evolution of a recombinase
Schatz, D. G. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2004.08.004 · Cited by 76 · see citing works
Autoubiquitylation of the V(D)J recombinase protein RAG1
Jones, J. M., & Gellert, M. F. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2637012100 · Cited by 76 · see citing works
Functional characterization of an active Rag-like transposase
Hencken, C. G., Li, X., & Craig, N. L. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2338 · Cited by 75 · see citing works
Prokaryote and eukaryote evolvability
Poole, A. M., Phillips, M. J., & Penny, D. (2003) · Biosystems · doi:10.1016/s0303-2647(02)00131-4 · Cited by 76 · see citing works
Joining-Deficient RAG1 Mutants Block V(D)J Recombination In Vivo and Hairpin Opening In Vitro
Schultz, H. Y., Landree, M. A., Qiu, J., Kale, S. B., & Roth, D. B. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00155-1 · Cited by 75 · see citing works
Self-citation
Homeostatically proliferating CD4 T cells are involved in the pathogenesis of an Omenn syndrome murine model.
Khiong, K., Murakami, M., Kitabayashi, C., Ueda, N., Sawa, S.-I., Sakamoto, A., Kotzin, B., Rozzo, S., Ishihara, K., Verella-Garcia, M., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30513 · Cited by 82 · see citing works
The Sleeping Beauty Transposable Element: Evolution, Regulation and Genetic Applications
Ivics, Z., Kaufman, C. D., Zayed, H., Miskey, C., Walisko, O., & Izsvák, Z. (2004) · Current Issues in Molecular Biology · doi:10.21775/cimb.006.043 · Cited by 72 · see citing works
Biochemistry of V(D)J Recombination
Schatz, D. G., & Spanopoulou, E. (2005) · Springer eBooks · doi:10.1007/3-540-26363-2_4 · Cited by 72 · see citing works
Identification of catalytic metal ion ligands in ribozymes
Frederiksen, J. K., & Piccirilli, J. A. (2009) · Methods · doi:10.1016/j.ymeth.2009.07.005 · Cited by 72 · see citing works
The Role of Recombination Activating Gene (RAG) Reinduction in Thymocyte Development in Vivo
Yannoutsos, N., Wilson, P. C., Yu, W., Chen, H. T., Nussenzweig, A., Petrie, H. T., & Nussenzweig, M. C. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.4.471 · Cited by 71 · see citing works
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
Santagata, S., Gomez, C. A., Sobacchi, C., Bozzi, F., Abinun, M., Pašić, S., Cortés, P., Vezzoni, P., & VILLA, A. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.26.14572 · Cited by 69 · see citing works
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
Huye, L. E., Purugganan, M. M., Jiang, M., & Roth, D. B. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.10.3460-3473.2002 · Cited by 69 · see citing works
Self-citation
RAG1/2-Mediated Resolution of Transposition Intermediates
Melek, M., & Gellert, M. F. (2000) · Cell · doi:10.1016/s0092-8674(00)80874-0 · Cited by 66 · see citing works
Mutations in Conserved Regions of the Predicted RAG2 Kelch Repeats Block Initiation of V(D)J Recombination and Result in Primary Immunodeficiencies
Gomez, C. A., Ptaszek, L. M., VILLA, A. M., Bozzi, F., Sobacchi, C., Brooks, E. G., Notarangelo, L. D., Spanopoulou, E., Pan, Z. Q., Vezzoni, P., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.15.5653-5664.2000 · Cited by 64 · see citing works
RAG gene defects at the verge of immunodeficiency and immune dysregulation
VILLA, A. M., & Notarangelo, L. D. (2018) · Immunological Reviews · doi:10.1111/imr.12713 · Cited by 64 · see citing works
Sleeping Beauty Transposition
Ivics, Z., & Izsvák, Z. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mdna3-0042-2014 · Cited by 64 · see citing works
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
Swanson, P. C. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.2.449-458.2001 · Cited by 60 · see citing works
Identification of Two Topologically Independent Domains in RAG1 and Their Role in Macromolecular Interactions Relevant to V(D)J Recombination
Arbuckle, J. L., Fauss, L., Simpson, R., Ptaszek, L. M., & Rodgers, K. K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105988200 · Cited by 57 · see citing works
Identification of Basic Residues in RAG2 Critical for DNA Binding by the RAG1-RAG2 Complex
Fugmann, S. D., & Schatz, D. G. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00352-5 · Cited by 55 · see citing works
Initial Stages of V(D)J Recombination: The Organization of RAG1/2 and RSS DNA in the Postcleavage Complex
Grundy, G. J., Ramón‐Maiques, S., Dimitriadis, E. K., Kotova, S., Biertümpfel, C., Heymann, J. B., Steven, A. C., Gellert, M. F., & Yang, W. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.06.022 · Cited by 52 · see citing works
Cooperative recruitment of HMGB1 during V(D)J recombination through interactions with RAG1 and DNA
Little, A. J., Corbett, E., Ortega, F. E., & Schatz, D. G. (2013) · Nucleic Acids Research · doi:10.1093/nar/gks1461 · Cited by 51 · see citing works
P Transposable Elements inDrosophilaand other Eukaryotic Organisms
Majumdar, S., & Rio, D. C. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mdna3-0004-2014 · Cited by 51 · see citing works
Putting the pieces together: identification and characterization of structural domains in the V(D)J recombination protein RAG1
De, P., & Rodgers, K. K. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00154.x · Cited by 50 · see citing works
P Transposable Elements inDrosophila melanogaster
Rio, D. C. (2007) · doi:10.1128/9781555817954.ch21 · Cited by 49 · see citing works
Definition of Minimal Domains of Interaction Within the Recombination-Activating Genes 1 and 2 Recombinase Complex
Aidinis, V., Dias, D. C., Gomez, C. A., Bhattacharyya, D., Spanopoulou, E., & Santagata, S. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.11.5826 · Cited by 47 · see citing works
The V(D)J Recombinase Efficiently Cleaves and Transposes Signal Joints
Neiditch, M. B., Lee, G. S., Huye, L. E., Brandt, V. L., & Roth, D. B. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00494-x · Cited by 46 · see citing works
Self-citation
Effect of HIV integrase inhibitors on the RAG1/2 recombinase
Melek, M., Jones, J. M., O'Dea, M. H., Pais, G. C. G., Burke, T. R., Pommier, Y. G., Neamati, N., & Gellert, M. F. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012610699 · Cited by 46 · see citing works
Artemis sheds new light on V(D)J recombination
Deist, F. L., Poinsignon, C., Moshous, D., Fischer, A., & de Villartay, J. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00169.x · Cited by 45 · see citing works
RAG2’s Acidic Hinge Restricts Repair-Pathway Choice and Promotes Genomic Stability
Coussens, M., Wendland, R. L., Deriano, L., Lindsay, C., Arnal, S. M., & Roth, D. B. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.07.041 · Cited by 44 · see citing works
Self-citation
Mutational analysis of highly conserved aspartate residues essential to the catalytic core of the piggyBac transposase
Keith, J. H., Schaeper, C. A., Fraser, T. S., & Fraser, M. J. (2008) · BMC Molecular Biology · doi:10.1186/1471-2199-9-73 · Cited by 44 · see citing works
Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway
Cui, X., & Meek, K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610928104 · Cited by 43 · see citing works
Two distinct long-range synaptic complexes promote different aspects of end processing prior to repair of DNA breaks by non-homologous end joining
Buehl, C. J., Goff, N. J., Hardwick, S. W., Gellert, M. F., Blundell, T. L., Yang, W., Chaplin, A. K., & Meek, K. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.01.012 · Cited by 41 · see citing works
Identification and Analysis of a Hyperactive Mutant Form of Drosophila P-Element Transposase
Beall, E. L., Mahoney, M. B., & Rio, D. C. (2002) · Genetics · doi:10.1093/genetics/162.1.217 · Cited by 40 · see citing works
Higher-Order Looping and Nuclear Organization of Tcra Facilitate Targeted RAG Cleavage and Regulated Rearrangement in Recombination Centers
Chaumeil, J., Micsinai, M., Ntziachristos, P., Deriano, L., Wang, J. M.-H., Ji, Y., Nora, E. P., Rodesch, M. J., Jeddeloh, J. A., Aifantis, I., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.01.024 · Cited by 40 · see citing works
The RAG2 C-terminus and ATM protect genome integrity by controlling antigen receptor gene cleavage
Chaumeil, J., Micsinai, M., Ntziachristos, P., Roth, D. B., Aifantis, I., Kluger, Y., Deriano, L., & Skok, J. A. (2013) · Nature Communications · doi:10.1038/ncomms3231 · Cited by 39 · see citing works
Self-citation
Temporal and spatial regulatory functions of the V(D)J recombinase
Desiderio, S. V. (2010) · Seminars in Immunology · doi:10.1016/j.smim.2010.09.001 · Cited by 39 · see citing works
The Central Domain of Core RAG1 Preferentially Recognizes Single-stranded Recombination Signal Sequence Heptamer
Peak, M. M., Arbuckle, J. L., & Rodgers, K. K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302041200 · Cited by 39 · see citing works
Overlapping Signals for Protein Degradation and Nuclear Localization Define a Role for Intrinsic RAG-2 Nuclear Uptake in Dividing Cells
Ross, A. E., Vuica, M., & Desiderio, S. V. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.15.5308-5319.2003 · Cited by 39 · see citing works
Amino acid residues in Rag1 crucial for DNA hairpin formation
Lu, C. P.-J., Sandoval, H., Brandt, V. L., Rice, P. A., & Roth, D. B. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1154 · Cited by 38 · see citing works
Self-citation
A C-Terminal Region of RAG1 Contacts the Coding DNA during V(D)J Recombination
Mo, X., Tu, B., & Sadofsky, M. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.6.2038-2047.2001 · Cited by 37 · see citing works
Cloning of shark RAG2 and characterization of the RAG1/RAG2 gene locus
Schluter, S. F., & Marchalonis, J. J. (2003) · The FASEB Journal · doi:10.1096/fj.02-0565fje · Cited by 36 · see citing works
RAG1 and RAG2 in V(D)J Recombination and Transposition
Fugmann, S. D. (2001) · Immunologic Research · doi:10.1385/ir:23:1:23 · Cited by 34 · see citing works
V(D)J Recombination
Gellert, M. F. (2007) · doi:10.1128/9781555817954.ch29 · Cited by 33 · see citing works
Recombination‐activating gene proteins: more regulation, please
Sadofsky, M. J. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00164.x · Cited by 31 · see citing works
A recombinase diversified: new functions of the RAG proteins
Brandt, V. L., & Roth, D. B. (2002) · Current Opinion in Immunology · doi:10.1016/s0952-7915(02)00325-4 · Cited by 31 · see citing works
Self-citation
Conditional RAG-1 Mutants Block the Hairpin Formation Step of V(D)J Recombination
Kale, S. B., Landree, M. A., & Roth, D. B. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.2.459-466.2001 · Cited by 31 · see citing works
Self-citation
The PHD domain of the sea urchin RAG2 homolog, SpRAG2L, recognizes dimethylated lysine 4 in histone H3 tails
Wilson, D. R., Norton, D. D., & Fugmann, S. D. (2008) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2008.03.012 · Cited by 30 · see citing works
RAG and HMGB1 create a large bend in the 23RSS in the V(D)J recombination synaptic complexes
Ciubotaru, M., Trexler, A., Spiridon, L. N., Surleac, M. D., Rhoades, E. R., Petrescu, A., & Schatz, D. G. (2013) · Nucleic Acids Research · doi:10.1093/nar/gks1294 · Cited by 30 · see citing works
Engineered Sleeping Beauty transposase redirects transposon integration away from genes
Miskey, C., Kesselring, L., Querques, I., Abrusán, G., Barábas, O., & Ivics, Z. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac092 · Cited by 28 · see citing works
Non-consensus heptamer sequences destabilize the RAG post-cleavage complex, making ends available to alternative DNA repair pathways
Arnal, S. M., Holub, A. J., Salus, S. S., & Roth, D. B. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp1252 · Cited by 29 · see citing works
Self-citation
Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability
Kirkham, C. M., Scott, J. N. F., Wang, X., Smith, A., Kupinski, A. P., Ford, A. M., Westhead, D. R., Stockley, P. G., Tůma, R., & Boyes, J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.02.025 · Cited by 29 · see citing works
V(D)J Recombination: Site-specific Cleavage and Repair
Kim, D. R., Park, S. J., & Oettinger, M. A. (2000) · Molecules and Cells · doi:10.1016/s1016-8478(23)17488-7 · Cited by 29 · see citing works

Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase
Kim, D. R., Dai, Y., Mundy, C. L., Yang, W., & Oettinger, M. A. (1999) · Genes & Development · doi:10.1101/gad.13.23.3070 · Cited by 199 · see citing works
Amino Acid Residues in RAG1 Responsible for the Interaction with RAG2 during the V(D)J Recombination Process
Ko, J. E., Kim, C. W., & Kim, D. R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311471200 · Cited by 9 · see citing works
Single Active Site That Catalyzes the Nicking and Transesterification Steps of V(D)J Recombination
Swanson, P. C. (2000)
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
Swanson, P. C. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.2.449-458.2001 · Cited by 60 · see citing works
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
Huye, L. E., Purugganan, M. M., Jiang, M., & Roth, D. B. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.10.3460-3473.2002 · Cited by 69 · see citing works
Self-citation

Authors: Landree, M. A., Wibbenmeyer, J. A., & Roth, D. B.
Affiliations: Baylor College of Medicine (US)
Howard Hughes Medical Institute (US)
Corresponding author: Roth, D. B.
ORCID: Roth, D. B.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 1999-12-01
Volume: 13
Issue: 23
Pages: 3059-3069
ISSN: 0890-9369 (ISSN-L)
DOI: 10.1101/gad.13.23.3059
PMC: PMC317185
OpenAlex: W2075932264
Cited by: 209
References: 73
Citations by year: 2026: 1 · 2025: 1 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 1 · 2020: 1 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 15 · 2014: 9 · 2013: 7 · 2012: 6
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (GM08231, T32GM008231)
National Institute of Allergy and Infectious Diseases (T32AI007495, AI07495, AI 36420, R01AI036420)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: RAG1, RAG2, V(D)J recombination, DNA double-strand breaks, nicking, hairpin formation, transesterification, catalytic site, acidic amino acids, site-directed mutagenesis, lymphocyte development
MeSH terms: Amino Acid Sequence, Animals, Binding Sites, Catalysis, Cricetulus, Cysteine, DNA, DNA Nucleotidyltransferases, DNA-Binding Proteins, Cricetinae, Humans, Lymphocytes, Manganese, Molecular Sequence Data, Nuclear Proteins, Recombinant Fusion Proteins, Structure-Activity Relationship, Transfection, Vertebrates, Gene Rearrangement, Mutagenesis, Site-Directed, Sequence Alignment, CHO Cells, Sequence Homology, Amino Acid, Homeodomain Proteins, Amino Acid Substitution, Catalytic Domain, VDJ Recombinases

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Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination

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