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Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase
Open accessAbstract
The RAG1 and RAG2 proteins collaborate to initiate V(D)J recombination by binding recombination signal sequences (RSSs) and making a double-strand break between the RSS and adjacent coding DNA. Like the reactions of their biochemical cousins, the bacterial transposases and retroviral integrases, cleavage by the RAG proteins requires a divalent metal ion but does not involve a covalent protein/DNA intermediate. In the transposase/integrase family, a triplet of acidic residues, commonly called a DDE motif, is often found to coordinate the metal ion used for catalysis. We show here that mutations in each of three acidic residues in RAG1 result in mutant derivatives that can bind the RSS but whose ability to catalyze either of the two chemical steps of V(D)J cleavage (nicking and hairpin formation) is severely impaired. Because both chemical steps are affected by the same mutations, a single active site appears responsible for both reactions. Two independent lines of evidence demonstrate that at least two of these acidic residues are directly involved in coordinating a divalent metal ion: The substitution of Cys for Asp allows rescue of some catalytic function, whereas an alanine substitution is no longer subject to iron-induced hydroxyl radical cleavage. Our results support a model in which the RAG1 protein contains the active site of the V(D)J recombinase and are interpreted in light of predictions about the structure of RAG1.
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“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 [21]
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Items 101–199 of 199
Identification and Characterization of a Gain-of-Function RAG-1 Mutant
Kriatchko, A. N., Anderson, D. K., & Swanson, P. C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02487-05 · Cited by 28
“The E649A RAG-1 mutation is located within the central domain of RAG-1 (8), which encompasses two residues critical for the catalytic activity of the recombinase, D600 and D708 (12, 21, 24).”
BackgroundRetroviral Integrase: Then and Now
Andrake, M., & Skalka, A. M. (2015) · Annual Review of Virology · doi:10.1146/annurev-virology-100114-055043 · Cited by 34
Godderz, L. J. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg281 · Cited by 28
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“Similar studies have been carried out on other RNase H-like superfamily members, such as Tn7 TnsA (31), Tn10 transposase (28) and RAG1 (29,30).”
Requirements for DNA hairpin formation by RAG1/2
Grundy, G. J., Hesse, J. E., & Gellert, M. F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611293104 · Cited by 26
Bischerour, J., Lu, C. P.-J., Roth, D. B., & Chalmers, R. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00187-09 · Cited by 26
“This evidence placed RAG1 firmly within the family of transposases and retroviral integrases that have a characteristic DDE triad of amino acid residues that coordinate catalytic metal ions in the active site (1, 26, 30, 35, 39, 46).”
BackgroundThe Mechanism of V(D)J Recombination
Little, A. J., Matthews, A. G. W., Oettinger, M. A., Roth, D. B., & Schatz, D. G. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397933-9.00002-3 · Cited by 27
Self-citationZhang, Y., Shetty, K. S., Surleac, M. D., Petrescu, A., & Schatz, D. G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.638627 · Cited by 25
“Finally, our findings regarding the importance of Asp546 and Glu-547 for the RAG1-RAG2 interaction and for V(D)J recombination agree with previous biochemical studies (22, 47).”
ResultIdentification and Mutational Analysis of Mg2+ Binding Site in EcoP15I DNA Methyltransferase
Bist, P., & Rao, D. N. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307053200 · Cited by 25
Arbuckle, J. L., Rahman, N. S., Zhao, S., Rodgers, W., & Rodgers, K. K. (2011) · BMC Biochemistry · doi:10.1186/1471-2091-12-23 · Cited by 24
“Besides the ability to recognize the RSS nonamer and heptamer through the NBD [19,21,22] and the central domain [20,23], respectively, core RAG1 contains the essential acidic active site residues [24-26].”
BackgroundV(D)J recombination: how to tame a transposase
Brandt, V. L., & Roth, D. B. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00161.x · Cited by 24
“Further confirmation that the two D residues contact the catalytic metal was provided by elegant iron-induced OH radical protein cleavage experiments (35).”
BackgroundRAG Transposase Can Capture and Commit to Target DNA before or after Donor Cleavage
Neiditch, M. B., Lee, G. S., Landree, M. A., & Roth, D. B. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.13.4302-4310.2001 · Cited by 24
“Recombinant truncated (core) RAG proteins (amino acids 384 to 1008 of RAG1 and 1 to 387 of RAG2) were purified from baculovirus-infected insect cells as previously described (3, 19, 25, 41).”
BackgroundInfluentialNagawa, F., Kodama, M., Nishihara, T., Ishiguro, K., & Sakano, H. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.20.7217-7225.2002 · Cited by 23
“In order to study the effect of DDE mutations of RAG1 on the RSS-RAG interaction, we then analyzed the precleavage complex formed with the D708N mutant protein (11, 19, 20).”
MethodFeng, B., Bulchand, S., Yaksi, E., Friedrich, R. W., & Jesuthasan, S. J. (2005) · BMC Neuroscience · doi:10.1186/1471-2202-6-46 · Cited by 22
“RAG1 contains the active site for V(D)J recombination [33,34] and can cleave DNA in vitro on its own, although it does so with low efficiency [35].”
Joining Mutants of RAG1 and RAG2 that Demonstrate Impaired Interactions with the Coding-end DNA
Nagawa, F., Hirose, S., Nishizumi, H., Nishihara, T., & Sakano, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405485200 · Cited by 22
Functional Organization of Single and Paired V(D)J Cleavage Complexes
Landree, M. A., Kale, S. B., & Roth, D. B. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.13.4256-4264.2001 · Cited by 22
“either nicking or hairpin formation (7, 12, 14).”
BackgroundMethodAn Integrated Look at Metallonuclease Mechanism
Dupureur, C. M. (2008) · Current Chemical Biology · doi:10.2174/187231308784220491 · Cited by 21
Assembly Pathway and Characterization of the RAG1/2-DNA Paired and Signal-end Complexes
Lapkouski, M., Chuenchor, W., Kim, M., Gellert, M. F., & Yang, W. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.641787 · Cited by 21
Self-citationGershan, J. A. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.21.4105 · Cited by 20
DNA Cleavage Activity of the V(D)J Recombination Protein RAG1 Is Autoregulated
De, P., Peak, M. M., & Rodgers, K. K. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.15.6850-6860.2004 · Cited by 20
“Core RAG1 was previously reported to contain the active site for both nicking and hairpin formation, formed by two essential aspartate residues at positions 600 and 708 (13, 23, 24) and a glutamate at position 962 (23, 24).”
BackgroundResultInfluentialV(D)J recombination and DNA repair: lessons from human immune deficiencies and other animal models
de Villartay, J. (2002) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/00130832-200212000-00001 · Cited by 19
Kesselring, L., Miskey, C., Zuliani, C., Querques, I., Kapitonov, V. V., Laukó, A., Fehér, A., Palazzo, A. J., Diem, T., Lustig, J., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz1119 · Cited by 18
Early Steps of V(D)J Rearrangement: Insights from Biochemical Studies of RAG-RSS Complexes
Swanson, P. C., Kumar, S., & Raval, P. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-0296-2_1 · Cited by 17
Novel molecular mechanism for generating NK‐cell fitness and memory
Karo, J. M., & Sun, J. C.-Y. (2015) · European Journal of Immunology · doi:10.1002/eji.201445339 · Cited by 17
The DDE recombinases: diverse roles in acquired and innate immunity
Dreyfus, D. H. (2006) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)61083-6 · Cited by 17
Recombinase activating gene enzymes of lymphocytes
Notarangelo, L. D., Santagata, S., & VILLA, A. M. (2001) · Current Opinion in Hematology · doi:10.1097/00062752-200101000-00008 · Cited by 17
A Zinc Site in the C-Terminal Domain of RAG1 Is Essential for DNA Cleavage Activity
Gwyn, L. M., Peak, M. M., De, P., Rahman, N. S., & Rodgers, K. K. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.05.076 · Cited by 16
Metabolic sensor AMPK directly phosphorylates RAG1 protein and regulates V(D)J recombination
Um, J., Brown, A. L., Singh, S. K., Chen, Y., Guček, M., Lee, B.-S., Luckey, M. A., Kim, M. K., Park, J., Sleckman, B. P., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1307928110 · Cited by 17
“Incubation of purified RAG complex with 12-RSS and 23-RSS oligonucleotides in the presence of a divalent metal cation such as Mg or Mn can induce nick and hairpin formation (19, 29, 30).”
Ciubotaru, M., & Schatz, D. G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.19.8727-8744.2004 · Cited by 16
Assessing a Theoretical Risk of Dolutegravir-Induced Developmental Immunotoxicity in Juvenile Rats
Rhodes, M., Laffan, S. B., Genell, C. A., Gower, J., Maier, C. C., Fukushima, T., Nichols, G., & Bassiri, A. E. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs220 · Cited by 16
“Given these similarities coupled with the fact that both enzymes share a common active site motif (Kim et al., 1999), it is theoretically possible that INIs might impact the activity of RAG1/2.”
BackgroundOrdered DNA release and target capture in RAG transposition
Matthews, A. G. W., Elkin, S. K., & Oettinger, M. A. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600131 · Cited by 16
“Oligonucleotide sequences for VDJ100, VDJ101, VDJ132, VDJ133, VDJ104, VDJ106, YD24, and VDJ134 are described in Cuomo et al (1996) and Kim et al (1999).”
Self-citationLi, W., Chang, F.-C., & Desiderio, S. V. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.12.3935-3946.2001 · Cited by 15
“This was borne out by evidence that residues D600, D708, and E962 of RAG-1 play an intimate role in catalysis of DNA cleavage (14, 23, 27).”
BackgroundInfluentialMaitra, R., & Sadofsky, M. J. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp192 · Cited by 14
“The core region contains the acidic residues essential for the nuclease activity (25,26) and known DNA-binding behavior.”
Haniford, D. B. (2007) · doi:10.1128/9781555817954.ch20 · Cited by 13
Nishihara, T., Nagawa, F., Imai, T., & Sakano, H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m709890200 · Cited by 12
The architecture of the 12RSS in V(D)J recombination signal and synaptic complexes
Ciubotaru, M., Surleac, M. D., Metskas, L. A., Koo, P. K., Rhoades, E. R., Petrescu, A., & Schatz, D. G. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1348 · Cited by 12
DNA-dependent Protein Kinase Mediates V(D)J Recombination via RAG2 Phosphorylation
Hah, Y., Lee, J.-H., & Kim, D. R. (2007) · BMB Reports · doi:10.5483/bmbrep.2007.40.3.432 · Cited by 12
“vaccinia viral system as previously described (Kim et al., 1999) was heavily phosphorylated by purified DNA-PK proteins in the presence of DNA (Fig.”
BackgroundMethodInfluentialSelf-citationHahm, J. R., Jung, T. S., Byun, S. Y., Lee, Y. N., Lee, K. H., & Kim, D. R. (2004) · Metabolism · doi:10.1016/j.metabol.2004.05.018 · Cited by 11
Self-citationCompound Heterozygous Mutation of Rag1 Leading to Omenn Syndrome
Matthews, A. G. W., Briggs, C. E., Yamanaka, K., Small, T. N., Mooster, J. L., Bonilla, F. A., Oettinger, M. A., & Butte, M. J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121489 · Cited by 11
“There are four known functional elements within the Rag1 C-terminal domain: basic region IV (aa 829–843), which binds to the nuclear transport protein Rch1 [47]; the nuclear localization signal (aa 972–976) [48]; E965, which is one of three key active site residues [49,50]; and two zinc-binding sites (C905/C907 and H9…”
BackgroundSelf-citationA bifunctional DNA binding region in Tn5 transposase
Gradman, R. J., Ptacin, J. L., Bhasin, A., Reznikoff, W. S., & Goryshin, I. Y. (2007) · Molecular Microbiology · doi:10.1111/j.1365-2958.2007.06056.x · Cited by 11
“…motif has been discovered in a wide variety of other retroviral integrase superfamily proteins including the RAG1 protein of V(D)J recombination (Kim et al., 1999; Swanson, 2001; Brandt and Roth, 2004) and HIV-1 integrase (Rowland and Dyke, 1990; Engelman and Craigie, 1992; Kulkosky et al.,…”
BackgroundHewitt, S. L., Wong, J. B., Lee, J., Nishana, M., Chen, H., Coussens, M., Arnal, S. M., Blumenberg, L. M., Roth, D. B., Paull, T. T., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.084 · Cited by 11
“…gives rise to a similar defect, we used a recombination substrate to measure signal and coding joint formation (which usually occurs by classical NHEJ), including, as a negative control, the catalytically inactive RAG1 DDE mutant (Corneo et al., 2007; Kim et al., 1999; Landree et al., 1999).”
BackgroundMethodHaque, N., Kawai, T., Ratnasinghe, B. D., Wagenknecht, J. B., Urrutia, R. A., Notarangelo, L. D., & Zimmermann, M. T. (2023) · iScience · doi:10.1016/j.isci.2023.108040 · Cited by 10
Liu, Y., Zhang, L., & Desiderio, S. V. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-0296-2_13 · Cited by 10
The Origin of V(D)J Diversification
Hsu, E., & Lewis, S. M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397933-9.00009-6 · Cited by 10
Lu, C. P.-J., Posey, J. E., & Roth, D. B. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn128 · Cited by 10
Nuclease‐independent functions of RAG1 direct distinct DNA damage responses in B cells
Johnston, R., Mathias, B., Crowley, S. J., Schmidt, H. A., White, L. S., Mosammaparast, N., Green, A. M., & Bednarski, J. J. (2022) · EMBO Reports · doi:10.15252/embr.202255429 · Cited by 9
“…ligase catalytic site (RAG1 P326G , PG), and (iv) endonuclease-inactive RAG1 with D708A mutation within its catalytic domain (RAG1 D708A , DA; Fig 4A; Kim et al , 1999; Fugmann et al , 2000b; Dudley et al , 2003; Yurchenko et al , 2003; Simkus et al , 2007; Ji et al , 2010; Beilinson et al , 2021).”
Ko, J. E., Kim, C. W., & Kim, D. R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311471200 · Cited by 9
Self-citationRecruitment of RAG1 and RAG2 to Chromatinized DNA during V(D)J Recombination
Shetty, K. S., & Schatz, D. G. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00219-15 · Cited by 9
The ESC: The Dangerous By-Product of V(D)J Recombination
Smith, A., Scott, J. N. F., & Boyes, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01572 · Cited by 8
Kumar, A., Bhandari, A., Sarde, S. J., Muppavarapu, S., & Tandon, R. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.04.125 · Cited by 8
Recombination-activating gene 1 and 2 (RAG1 and RAG2) in flounder (Paralichthys olivaceus)
Wang, X., Tan, X., Zhang, P., Zhang, Y., & Xu, P. (2014) · Journal of Biosciences · doi:10.1007/s12038-014-9469-1 · Cited by 8
“…of the murine RAG1 1040 residues, a RING finger and zinc finger A (ZFA) in the zinc-binding dimerization domain, and a zinc finger B (ZFB) in the core region and a zinc site in the Cterminal domain (Kim et al. 1999; Landree et al. 1999; Fugmann et al. 2000; De and Rodgers 2004; Gwyn et al. 2009).”
Thermal dependency of RAG1 self-association properties
De, P., Zhao, S., Gwyn, L. M., Godderz, L. J., Peak, M. M., & Rodgers, K. K. (2008) · BMC Biochemistry · doi:10.1186/1471-2091-9-5 · Cited by 8
“RAG1 residues D600, D708, and E962 constitute the DDE motif active site, with these residues acting to coordinate the divalent metal cations essential for the DNA cleavage functions [14,15].”
BackgroundIn Vitro Processing of the 3′-Overhanging DNA in the Postcleavage Complex Involved in V(D)J Joining
Nishihara, T., Nagawa, F., Nishizumi, H., Kodama, M., Hirose, S., Hayashi, R., & Sakano, H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.9.3692-3702.2004 · Cited by 8
“In contrast to the wild-type control (WT), the SE complex containing the mutant RAG1 (D708A) failed to generate any reaction products.”
BackgroundInfluentialHassaballa, A., Palmer, V., Anderson, D. K., Kassmeier, M. D., Nganga, V. K., Parks, K. W., Volkmer, D., Perry, G. A., & Swanson, P. C. (2011) · Immunology · doi:10.1111/j.1365-2567.2011.03509.x · Cited by 7
Adapting to a changing world: RAGgenomics and evolution
Camargo, M. M. D., & Nahum, L. A. (2005) · Human Genomics · doi:10.1186/1479-7364-2-2-132 · Cited by 7
“The RAG-1 protein contains a DDE motif (D600, D708 and E962), which is critical for both DNA cleavage and hairpin formation.(19,20,22)”
BackgroundDissertationes bioscientiarum molecularium Universitatis Helsingiensis in Viikki
Saariaho, A.-H., Hilden, T. J., & Alaranta, A. (2006) · Cited by 7
Dooner, H. K., & Weil, C. F. (2013) · doi:10.1002/9781118500156.ch8 · Cited by 6
The Mechanism, Regulation and Evolution of V(D)J Recombination
Schatz, D. G., Zhang, Y., Xiao, J., Zha, S., Zhang, Y., & Alt, F. W. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95895-0.00004-0 · Cited by 5
Diaby, M., Wu, H., Gao, B., Shi, S., Wang, B., Wang, S., Wang, Y., Wu, Z., Chen, C., Wang, X., et al. (2024) · Advanced Science · doi:10.1002/advs.202400969 · Cited by 4
Generation of a Manganese Specific Restriction Endonuclease with Nicking Activity
Vasu, K., Matheshwaran, S., Boggavarapu, R., & Nagaraja, V. (2010) · Biochemistry · doi:10.1021/bi101035k · Cited by 5
Analysis of recombination signal sequences in zebrafish
Danilova, N. (2005) · Molecular Immunology · doi:10.1016/j.molimm.2004.11.022 · Cited by 5
Sabogal, A., & Rio, D. C. (2010) · Protein Science · doi:10.1002/pro.499 · Cited by 5
“The C-terminus of the P-element transposase protein contains many acidic residues and is thought to belong to the RNase H-like superfamily of polynucleotidyl transferases, including the bacterial Tn5 transposase,(6) the Mos1 transposase,(7) the HIV-1 integrase,(8) the phage Mu transposase,(9) the Holliday junction nuc…”
BackgroundThe Mechanism of V(D)J Recombination
Sekiguchi, J., Alt, F. W., & Oettinger, M. A. (2004) · Elsevier eBooks · doi:10.1016/b978-012053641-2/50006-x · Cited by 5
Self-citationDifferent sea urchin RAG-like genes were domesticated to carry out different functions
Yakovenko, I., Tobi, D., Ner‐Gaon, H., & Oren, M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1066510 · Cited by 4
“Traditionally, both RAG proteins are subdivided into a “functional protein core” (384-1008 of RAG1 and 1-387 of RAG2 in mouse) that was proven to be able to carry out recombination on its own (40) and an N-terminal “non-core” regions.”
BackgroundKoning, M. T., Vletter, E. M., Rademaker, R., Vergroesen, R. D., Trollmann, I., Parren, P. W. H. I., van Bergen, C. A. M., Scherer, H. U., Kiełbasa, S. M., Toes, R. E. M., et al. (2020) · European Journal of Immunology · doi:10.1002/eji.202048828 · Cited by 4
Recombination Activating Gene 1 Product Alone Possesses Endonucleolytic Activity
Kim, D. R. (2003) · BMB Reports · doi:10.5483/bmbrep.2003.36.2.201 · Cited by 4
“In recent papers, these acidic residues of the V(D)J recombinase are found only in RAG1 (Kim et al., 1999; Landree et al., 1999; Fugmann et al., 2000).”
BackgroundSelf-citationGilbert, F. (2000) · Genetic Testing · doi:10.1089/109065700750065180 · Cited by 4
Comparison of immunophenotypes between Rag2 knockout mice derived from two different sources
Roh, Y. J., Gong, J. E., Kim, J. E., Jin, Y. J., Song, H. J., Seol, A., Park, J., Lim, Y., & Hwang, D. Y. (2023) · Laboratory Animal Research · doi:10.1186/s42826-023-00153-8 · Cited by 4
“This protein helps activate the endonuclease functions of Rag1 because it only binds to the DNA strand without endonuclease activity [3, 4].”
BackgroundChovatia, R. M., Acharya, A., Rasal, K. D., Bedekar, M. K., Jeena, K., Rathinam, R. B., Dinakaran, C., & Tripathi, G. (2024) · Gene Expression Patterns · doi:10.1016/j.gep.2024.119358 · Cited by 3
Modulation of RAG/DNA complex by HSP70 in V(D)J recombination
Son, Y. M., Lee, J. H., & Kim, D. R. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.10.132 · Cited by 3
Self-citationThe Origin of V(D)J Diversification
Lewis, S. M., Wu, G. E., & Hsu, E. (2004) · Elsevier eBooks · doi:10.1016/b978-012053641-2/50031-9 · Cited by 3
V(D)J Recombination: Mechanism and Consequences
Gellert, M. F. (2006) · Springer eBooks · doi:10.1007/4735_2006_0206 · Cited by 2
Saariaho, A.-H. (2006) · Työväentutkimus Vuosikirja · Cited by 2
DNA Transposons: Different Proteins and Mechanisms but Similar Rearrangements
Derbyshire, K. M., & Grindley, N. D. F. (2014) · ASM Press eBooks · doi:10.1128/9781555817640.ch26 · Cited by 2
Godderz, L. J., & Rodgers, K. K. (2004) · Journal of Spectroscopy · doi:10.1155/2004/572415 · Cited by 2
“A triad of acidic residues (Asp600, Asp708, and Glu962) called the DDE motif is located within core RAG1 [12,17,18].”
BackgroundCatalytic RAG1 mutants obstruct V(D)J recombination in vitro and in vivo
Furusawa, T., Hosoe, M., Ohkoshi, K., Takahashi, S., Kiyokawa, N., Fujimoto, J., Amemiya, H., Suzuki, S., & Tokunaga, T. (2003) · Molecular Immunology · doi:10.1016/s0161-5890(03)00008-7 · Cited by 2
Ivics, Z., & Izsvák, Z. (2015) · ASM Press eBooks · doi:10.1128/9781555819217.ch38 · Cited by 1
Retroviral Integrase Structure and DNA Recombination Mechanism
Engelman, A., & Peter, C. (2015) · ASM Press eBooks · doi:10.1128/9781555819217.ch44 · Cited by 2
Remdesivir may hinder the function of Recombination Activating Gene-1 (RAG1)
Lakshmanan, M., & Shabeer Ali, H. (2023) · Medical Hypotheses · doi:10.1016/j.mehy.2023.111228 · Cited by 1
Chromatin Folding and Recombination
Snetkova, V., & Skok, J. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-803480-4.00020-x · Cited by 1
The Origin of V(D)J Diversification
Hsu, E., & Lewis, S. M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-95895-0.00017-9 · Cited by 1
The Role of RAG in V(D)J Recombination
Carmona, L. M., & Schatz, D. G. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-374279-7.05012-8 · Cited by 1
ATM Deficiency -- A Multifaceted Defect in Lymphocyte Development
Helmink, B. A. (2012) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7k07291
Recombination Activating Genes, RAG1 and RAG2
Schatz, D. G. (2002) · Wiley Encyclopedia of Molecular Medicine · doi:10.1002/0471203076.emm0505
Poly(A)-Specific Ribonuclease PARN
National Cancer Institute (2020) · Definitions · doi:10.32388/sl2rwx
“Fenton chemistry has successfully been applied to map the divalent metal ion binding sites in many proteins (Cao and Barany, 1998; Ermacora et al., 1992; Ettner et al., 1995; Farber and Levine, 1986; Godson et al., 2000; Grodsky et al., 2000; Hlavaty et al., 2000; Hlavaty and Nowak, 1997; Huang et al., 2000; Kim et al…”
MethodNdikung, B. S. B. (2007) · DepositOnce · doi:10.14279/depositonce-1511
“Mutation analysis of RAG1 has identified three essential conserved amino acids; D600 and D708 play a role in metal binding and including E962 they are all required for V(D)J recombination (Fugmann et al., 2000; Kim et al., 1999; Landree et al., 1999).”
BackgroundThe rmal Dependency of RAG1 S elf-association Properties
De, P., Zhao, S., & Gwyn, L. M. (2008)
Rag1 D600A , a novel catalytically inactive RAG mouse modelPreprint
Wong, J. B., & Skok, J. A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/698332
Cut-and-run: a new mechanism by which V(D)J recombination could trigger leukaemia and lymphoma
Kirkham, C. M. (2014) · White Rose eTheses Online (University of Leeds, The University of Sheffield, University of York)
Zhang, M. (2009) · Creighton Digital Repository (CDR)
Schatz, D. G. (2010) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1346956.855076
Lieber, M. R. (2004) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1011614.213423
V(D)J recombination: mechanism and consequences
Gellert, M. F. (2007) · Topics in current genetics · doi:10.1007/978-3-540-71021-9_16
Faculty Opinions recommendation of Cracking the DNA code for V(D)J recombination.
Schatz, D. G. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733014924.793549792
RAG1: THE CORNERSTONE GENE INVOLVED IN VARIOUS IMMUNE DISEASES AND CANCERS
Fawzy, M., Nazmy, M., & Fathy, M. (2023) · Bulletin of Pharmaceutical Sciences Assiut · doi:10.21608/bfsa.2023.327556
The Role of RAG in V(D)J Recombination
Xiao, J., Martin, E. C., Wang, K., & Schatz, D. G. (2024) · Elsevier eBooks · doi:10.1016/b978-0-128-24465-4.00019-3
P Transposable Elements in Drosophila and other Eukaryotic Organisms
Majumdar, S., & Rio, D. C. (2015) · ASM Press eBooks · doi:10.1128/9781555819217.ch33
Metadata
- Authors
- Kim, D. R., Dai, Y., Mundy, C. L., Yang, W., & Oettinger, M. A.
- Affiliations
- National Institutes of Health (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1999-12-01
- Volume
- 13
- Issue
- 23
- Pages
- 3070-3080
- ISSN
- 0890-9369 (ISSN-L)
- PMC
- PMC317176
- OpenAlex
- W1984676925
- Cited by
- 199
- References
- 52
- Citations by year
- 2024: 4 · 2023: 5 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 16 · 2014: 8 · 2013: 6 · 2012: 6
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research Institute
- National Institutes of Health
- National Institute of General Medical Sciences (GM58026)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- RAG1, RAG2, V(D)J recombination, recombination signal sequences, acidic residues, active site, nicking, hairpin formation, immunoglobulin gene rearrangement
- MeSH terms
- Amino Acid Sequence, Animals, Aspartic Acid, Binding Sites, DNA Nucleotidyltransferases, DNA-Binding Proteins, HeLa Cells, Humans, Iron, Manganese, Molecular Sequence Data, Nuclear Proteins, Phenotype, Protein Binding, Recombinant Fusion Proteins, Structure-Activity Relationship, Gene Rearrangement, Mutagenesis, Site-Directed, Protein Structure, Secondary, Protein Structure, Tertiary, Hydroxyl Radical, Homeodomain Proteins, Amino Acid Substitution, Catalytic Domain, VDJ Recombinases, Mice
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