Regulation and Evolution of the RAG Recombinase

Advances in Immunology

Volumn 128, Issue , 2015, Pages 1-39

  Teng, Grace ^a   Schatz, David G ^a,b  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

Adaptive immunity; Cryptic RSS; Genome instability; RAG1; RAG2; Transposon; V(D)J recombination

Indexed keywords

HISTONE H3; RAG1 PROTEIN; RAG2 PROTEIN; RECOMBINASE; LYMPHOCYTE ANTIGEN RECEPTOR;

AMINO TERMINAL SEQUENCE; CARBOXY TERMINAL SEQUENCE; DNA BINDING; DNA END JOINING REPAIR; ENZYME REGULATION; GENE REARRANGEMENT; GENETIC RECOMBINATION; GENETIC STABILITY; HUMAN; MOLECULAR EVOLUTION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CLEAVAGE; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; RECOMBINATION SIGNAL SEQUENCE; SEQUENCE ANALYSIS; STRUCTURE ACTIVITY RELATION; UBIQUITINATION; VDJ RECOMBINATION; ANIMAL; CHEMISTRY; GENETICS; METABOLISM;

ANIMALS; EVOLUTION, MOLECULAR; HUMANS; RECEPTORS, ANTIGEN; RECOMBINASES; V(D)J RECOMBINATION;

EID: 84939188867     PISSN: 00652776     EISSN: 15578445     Source Type: Book Series    
DOI: 10.1016/bs.ai.2015.07.002     Document Type: Chapter

References (191)

1. Agrawal A., Eastman Q.M., Schatz D.G. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 1998, 394(6695):744-751. 10.1038/29457.
2. Agrawal A., Schatz D.G. RAG1 and RAG2 form a stable postcleavage synaptic complex with DNA containing signal ends in V(D)J recombination. Cell 1997, 89(1):43-53.
3. Akamatsu Y., Oettinger M.A. Distinct roles of RAG1 and RAG2 in binding the V(D)J recombination signal sequences. Molecular and Cellular Biology 1998, 18(8):4670-4678.
4. Alt F.W., Zhang Y., Meng F.L., Guo C., Schwer B. Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell 2013, 152(3):417-429. 10.1016/j.cell.2013.01.007.
5. Aravind L., Landsman D. AT-hook motifs identified in a wide variety of DNA-binding proteins. Nucleic Acids Research 1998, 26(19):4413-4421.
6. Arbuckle J.L., Fauss L.A., Simpson R., Ptaszek L.M., Rodgers K.K. Identification of two topologically independent domains in RAG1 and their role in macromolecular interactions relevant to V(D)J recombination. The Journal of Biological Chemistry 2001, 276(40):37093-37101. 10.1074/jbc.M105988200.
7. Arbuckle J.L., Rahman N.S., Zhao S., Rodgers W., Rodgers K.K. Elucidating the domain architecture and functions of non-core RAG1: The capacity of a non-core zinc-binding domain to function in nuclear import and nucleic acid binding. BMC Biochemistry 2011, 12:23. 10.1186/1471-2091-12-23.
8. Arnal S.M., Holub A.J., Salus S.S., Roth D.B. Non-consensus heptamer sequences destabilize the RAG post-cleavage complex, making ends available to alternative DNA repair pathways. Nucleic Acids Research 2010, 38(9):2944-2954. 10.1093/nar/gkp1252.
9. Ashworth T.D., Pear W.S., Chiang M.Y., Blacklow S.C., Mastio J., Xu L., et al. Deletion-based mechanisms of Notch1 activation in T-ALL: Key roles for RAG recombinase and a conserved internal translational start site in Notch1. Blood 2010, 116(25):5455-5464. 10.1182/blood-2010-05-286328.
10. Banerjee J.K., Schatz D.G. Synapsis alters RAG-mediated nicking at Tcrb recombination signal sequences: Implications for the "beyond 12/23" rule. Molecular and Cellular Biology 2014, 34(14):2566-2580. 10.1128/MCB.00411-14.
11. Bassing C.H., Alt F.W., Hughes M.M., D'Auteuil M., Wehrly T.D., Woodman B.B., et al. Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule. Nature 2000, 405(6786):583-586. 10.1038/35014635.
12. Bassing C.H., Whitlow S., Mostoslavsky R., Yang-Iott K., Ranganath S., Alt F.W. Vbeta cluster sequences reduce the frequency of primary Vbeta2 and Vbeta14 rearrangements. European Journal of Immunology 2008, 38(9):2564-2572. 10.1002/eji.200838347.
13. Bednarski J.J., Nickless A., Bhattacharya D., Amin R.H., Schlissel M.S., Sleckman B.P. RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation. The Journal of Experimental Medicine 2012, 209(1):11-17. 10.1084/jem.20112078.
14. Bellon S.F., Rodgers K.K., Schatz D.G., Coleman J.E., Steitz T.A. Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster. Nature Structural Biology 1997, 4(7):586-591.
15. Borghesi L., Hsu L.Y., Miller J.P., Anderson M., Herzenberg L., Herzenberg L., et al. B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors. The Journal of Experimental Medicine 2004, 199(4):491-502. 10.1084/jem.20031800.
16. Bowen S., Wangsa D., Ried T., Livak F., Hodes R.J. Concurrent V(D)J recombination and DNA end instability increase interchromosomal trans-rearrangements in ATM-deficient thymocytes. Nucleic Acids Research 2013, 41(8):4535-4548. 10.1093/nar/gkt154.
17. Brady B.L., Steinel N.C., Bassing C.H. Antigen receptor allelic exclusion: An update and reappraisal. Journal of Immunology 2010, 185(7):3801-3808. 10.4049/jimmunol.1001158.
18. Branzei D., Foiani M. Regulation of DNA repair throughout the cell cycle. Nature Reviews. Molecular Cell Biology 2008, 9(4):297-308. 10.1038/nrm2351.
19. Bredemeyer A.L., Helmink B.A., Innes C.L., Calderon B., McGinnis L.M., Mahowald G.K., et al. DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes. Nature 2008, 456(7223):819-823. 10.1038/nature07392.
20. Bredemeyer A.L., Sharma G.G., Huang C.Y., Helmink B.A., Walker L.M., Khor K.C., et al. ATM stabilizes DNA double-strand-break complexes during V(D)J recombination. Nature 2006, 442(7101):466-470. 10.1038/nature04866.
21. Buenrostro J.D., Giresi P.G., Zaba L.C., Chang H.Y., Greenleaf W.J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nature Methods 2013, 10(12):1213-1218. 10.1038/nmeth.2688.
22. Callebaut I., Mornon J.P. The V(D)J recombination activating protein RAG2 consists of a six-bladed propeller and a PHD fingerlike domain, as revealed by sequence analysis. Cellular and Molecular Life Sciences 1998, 54(8):880-891.
23. Callen E., Jankovic M., Difilippantonio S., Daniel J.A., Chen H.T., Celeste A., et al. ATM prevents the persistence and propagation of chromosome breaks in lymphocytes. Cell 2007, 130(1):63-75. 10.1016/j.cell.2007.06.016.
24. Chan E.A., Teng G., Corbett E., Choudhury K.R., Bassing C.H., Schatz D.G., et al. Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2. Proceedings of the National Academy of Sciences of the United States of America 2013, 110(48):E4628-E4637. 10.1073/pnas.1310846110.
25. Chao J., Rothschild G., Basu U. Ubiquitination events that regulate recombination of immunoglobulin Loci gene segments. Frontiers in Immunology 2014, 5:100. 10.3389/fimmu.2014.00100.
26. Chatterji M., Tsai C.L., Schatz D.G. Mobilization of RAG-generated signal ends by transposition and insertion in vivo. Molecular and Cellular Biology 2006, 26(4):1558-1568. 10.1128/MCB.26.4.1558-1568.2006.
27. Chaumeil J., Micsinai M., Ntziachristos P., Deriano L., Wang J.M., Ji Y., et al. Higher-order looping and nuclear organization of Tcra facilitate targeted rag cleavage and regulated rearrangement in recombination centers. Cell Reports 2013, 3(2):359-370. 10.1016/j.celrep.2013.01.024.
28. Chiarle R., Zhang Y., Frock R.L., Lewis S.M., Molinie B., Ho Y.J., et al. Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 2011, 147(1):107-119. 10.1016/j.cell.2011.07.049.
29. Choi J., Goh G., Walradt T., Hong B.S., Bunick C.G., Chen K.B., et al. Genomic landscape of cutaneous T cell lymphoma. Nature Genetics 2015, http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3356.html.
30. Choi N.M., Loguercio S., Verma-Gaur J., Degner S.C., Torkamani A., Su A.I., et al. Deep sequencing of the murine IgH repertoire reveals complex regulation of nonrandom V gene rearrangement frequencies. Journal of Immunology 2013, 191(5):2393-2402. 10.4049/jimmunol.1301279.
31. Cieslak A., Le Noir S., Trinquand A., Lhermitte L., Franchini D.M., Villarese P., et al. RUNX1-dependent RAG1 deposition instigates human TCR-delta locus rearrangement. The Journal of Experimental Medicine 2014, 211(9):1821-1832. 10.1084/jem.20132585.
32. Ciubotaru M., Surleac M.D., Metskas L.A., Koo P., Rhoades E., Petrescu A.J., et al. The architecture of the 12RSS in V(D)J recombination signal and synaptic complexes. Nucleic Acids Research 2015, 43(2):917-931. 10.1093/nar/gku1348.
33. Ciubotaru M., Trexler A.J., Spiridon L.N., Surleac M.D., Rhoades E., Petrescu A.J., et al. RAG and HMGB1 create a large bend in the 23RSS in the V(D)J recombination synaptic complexes. Nucleic Acids Research 2013, 41(4):2437-2454. 10.1093/nar/gks1294.
34. Cobb R.M., Oestreich K.J., Osipovich O.A., Oltz E.M. Accessibility control of V(D)J recombination. Advances in Immunology 2006, 91:45-109. 10.1016/S0065-2776(06)91002-5.
35. Cooper M.D., Alder M.N. The evolution of adaptive immune systems. Cell 2006, 124(4):815-822. 10.1016/j.cell.2006.02.001.
36. Corneo B., Benmerah A., Villartay J.P. A short peptide at the C terminus is responsible for the nuclear localization of RAG2. European Journal of Immunology 2002, 32(7):2068-2073. 10.1002/1521-4141(200207)32:7<2068::AID-IMMU2068>3.0.CO;2[-]6.
37. Corneo B., Wendland R.L., Deriano L., Cui X., Klein I.A., Wong S.Y., et al. Rag mutations reveal robust alternative end joining. Nature 2007, 449(7161):483-486. 10.1038/nature06168.
38. Coster G., Gold A., Chen D., Schatz D.G., Goldberg M. A dual interaction between the DNA damage response protein MDC1 and the RAG1 subunit of the V(D)J recombinase. The Journal of Biological Chemistry 2012, 287(43):36488-36498. 10.1074/jbc.M112.402487.
39. Coussens M.A., Wendland R.L., Deriano L., Lindsay C.R., Arnal S.M., Roth D.B. RAG2's acidic hinge restricts repair-pathway choice and promotes genomic stability. Cell Reports 2013, 4(5):870-878. 10.1016/j.celrep.2013.07.041.
40. Cowell L.G., Davila M., Kepler T.B., Kelsoe G. Identification and utilization of arbitrary correlations in models of recombination signal sequences. Genome Biology 2002, 3(12). RESEARCH0072.
41. Crosetto N., Mitra A., Silva M.J., Bienko M., Dojer N., Wang Q., et al. Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing. Nature Methods 2013, 10(4):361-365. 10.1038/nmeth.2408.
42. Cui X., Meek K. Linking double-stranded DNA breaks to the recombination activating gene complex directs repair to the nonhomologous end-joining pathway. Proceedings of the National Academy of Sciences of the United States of America 2007, 104(43):17046-17051. 10.1073/pnas.0610928104.
43. Cuomo C.A., Oettinger M.A. Analysis of regions of RAG-2 important for V(D)J recombination. Nucleic Acids Research 1994, 22(10):1810-1814.
44. Curry J.D., Schulz D., Guidos C.J., Danska J.S., Nutter L., Nussenzweig A., et al. Chromosomal reinsertion of broken RSS ends during T cell development. The Journal of Experimental Medicine 2007, 204(10):2293-2303. 10.1084/jem.20070583.
45. de Jong J., Akhtar W., Badhai J., Rust A.G., Rad R., Hilkens J., et al. Chromatin landscapes of retroviral and transposon integration profiles. PLoS Genetics 2014, 10(4):e1004250. 10.1371/journal.pgen.1004250.
46. Deininger, P. L., & Roy-Engel, A. M. (2002). Mobile DNA II (pp. 1080-1083). (N. L. Craig, R. Craigie, M. Gellert, & A. M. Lambowitz, Eds.). Washington, D.C.: ASM Press.
47. Deng Z., Liu H., Liu X. RAG1-mediated ubiquitylation of histone H3 is required for chromosomal V(D)J recombination. Cell Research 2015, 25(2):181-192. 10.1038/cr.2015.1.
48. Deriano L., Chaumeil J., Coussens M., Multani A., Chou Y., Alekseyenko A.V., et al. The RAG2 C terminus suppresses genomic instability and lymphomagenesis. Nature 2011, 471(7336):119-123. 10.1038/nature09755.
49. Deriano L., Roth D.B. Modernizing the nonhomologous end-joining repertoire: Alternative and classical NHEJ share the stage. Annual Review of Genetics 2013, 47:433-455. 10.1146/annurev-genet-110711-155540.
50. Difilippantonio M.J., McMahan C.J., Eastman Q.M., Spanopoulou E., Schatz D.G. RAG1 mediates signal sequence recognition and recruitment of RAG2 in V(D)J recombination. Cell 1996, 87(2):253-262.
51. Dorsett Y., Zhou Y., Tubbs A.T., Chen B.R., Purman C., Lee B.S., et al. HCoDES reveals chromosomal DNA end structures with single-nucleotide resolution. Molecular Cell 2014, 56(6):808-818. 10.1016/j.molcel.2014.10.024.
52. Drejer-Teel A.H., Fugmann S.D., Schatz D.G. The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Molecular and Cellular Biology 2007, 27(18):6288-6299. 10.1128/MCB.00835-07.
53. Dudley D.D., Sekiguchi J., Zhu C., Sadofsky M.J., Whitlow S., DeVido J., et al. Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice. The Journal of Experimental Medicine 2003, 198(9):1439-1450. 10.1084/jem.20030627.
54. Eastman Q.M., Villey I.J., Schatz D.G. Detection of RAG protein-V(D)J recombination signal interactions near the site of DNA cleavage by UV cross-linking. Molecular and Cellular Biology 1999, 19(5):3788-3797.
55. Ebert A., Medvedovic J., Tagoh H., Schwickert T.A., Busslinger M. Control of antigen receptor diversity through spatial regulation of V(D)J recombination. Cold Spring Harbor Symposia on Quantitative Biology 2013, 78:11-21. 10.1101/sqb.2013.78.019943.
56. Elkin S.K., Matthews A.G., Oettinger M.A. The C-terminal portion of RAG2 protects against transposition in vitro. The EMBO Journal 2003, 22(8):1931-1938. 10.1093/emboj/cdg184.
57. Feeney A.J., Goebel P., Espinoza C.R. Many levels of control of V gene rearrangement frequency. Immunological Reviews 2004, 200:44-56. 10.1111/j.0105-2896.2004.00163.x.
58. Flajnik M.F. Re-evaluation of the immunological Big Bang. Current Biology 2014, 24(21):R1060-R1065. 10.1016/j.cub.2014.09.070.
59. Fronkova E., Krejci O., Kalina T., Horvath O., Trka J., Hrusak O. Lymphoid differentiation pathways can be traced by TCR delta rearrangements. Journal of Immunology 2005, 175(4):2495-2500.
60. Fugmann S.D. The origins of the Rag genes-From transposition to V(D)J recombination. Seminars in Immunology 2010, 22(1):10-16. 10.1016/j.smim.2009.11.004.
61. Fugmann S.D., Lee A.I., Shockett P.E., Villey I.J., Schatz D.G. The RAG proteins and V(D)J recombination: Complexes, ends, and transposition. Annual Review of Immunology 2000, 18:495-527. 10.1146/annurev.immunol.18.1.495.
62. Fugmann S.D., Messier C., Novack L.A., Cameron R.A., Rast J.P. An ancient evolutionary origin of the Rag1/2 gene locus. Proceedings of the National Academy of Sciences of the United States of America 2006, 103(10):3728-3733. 10.1073/pnas.0509720103.
63. Fugmann S.D., Schatz D.G. Identification of basic residues in RAG2 critical for DNA binding by the RAG1-RAG2 complex. Molecular Cell 2001, 8(4):899-910.
64. Fugmann S.D., Villey I.J., Ptaszek L.M., Schatz D.G. Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complex. Molecular Cell 2000, 5(1):97-107.
65. Gangadharan S., Mularoni L., Fain-Thornton J., Wheelan S.J., Craig N.L. DNA transposon Hermes inserts into DNA in nucleosome-free regions in vivo. Proceedings of the National Academy of Sciences of the United States of America 2010, 107(51):21966-21972. 10.1073/pnas.1016382107.
66. Gapud E.J., Sleckman B.P. Unique and redundant functions of ATM and DNA-PKcs during V(D)J recombination. Cell Cycle 2011, 10(12):1928-1935.
67. Gigi V., Lewis S., Shestova O., Mijuskovic M., Deriano L., Meng W., et al. RAG2 mutants alter DSB repair pathway choice in vivo and illuminate the nature of 'alternative NHEJ'. Nucleic Acids Research 2014, 42(10):6352-6364. 10.1093/nar/gku295.
68. Golding A., Chandler S., Ballestar E., Wolffe A.P., Schlissel M.S. Nucleosome structure completely inhibits in vitro cleavage by the V(D)J recombinase. The EMBO Journal 1999, 18(13):3712-3723. 10.1093/emboj/18.13.3712.
69. Gopalakrishnan S., Majumder K., Predeus A., Huang Y., Koues O.I., Verma-Gaur J., et al. Unifying model for molecular determinants of the preselection Vbeta repertoire. Proceedings of the National Academy of Sciences of the United States of America 2013, 110(34):E3206-E3215. 10.1073/pnas.1304048110.
70. Gostissa M., Alt F.W., Chiarle R. Mechanisms that promote and suppress chromosomal translocations in lymphocytes. Annual Review of Immunology 2011, 29:319-350. 10.1146/annurev-immunol-031210-101329.
71. Grawunder U., Leu T.M., Schatz D.G., Werner A., Rolink A.G., Melchers F., et al. Down-regulation of RAG1 and RAG2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement. Immunity 1995, 3(5):601-608.
72. Grazini U., Zanardi F., Citterio E., Casola S., Goding C.R., McBlane F. The RING domain of RAG1 ubiquitylates histone H3: A novel activity in chromatin-mediated regulation of V(D)J joining. Molecular Cell 2010, 37(2):282-293. 10.1016/j.molcel.2009.12.035.
73. Green B., Bouchier C., Fairhead C., Craig N.L., Cormack B.P. Insertion site preference of Mu, Tn5, and Tn7 transposons. Mobile DNA 2012, 3(1):3. 10.1186/1759-8753-3-3.
74. Grundy G.J., Ramon-Maiques S., Dimitriadis E.K., Kotova S., Biertumpfel C., Heymann J.B., et al. Initial stages of V(D)J recombination: The organization of RAG1/2 and RSS DNA in the postcleavage complex. Molecular Cell 2009, 35(2):217-227. 10.1016/j.molcel.2009.06.022.
75. Grundy G.J., Yang W., Gellert M. Autoinhibition of DNA cleavage mediated by RAG1 and RAG2 is overcome by an epigenetic signal in V(D)J recombination. Proceedings of the National Academy of Sciences of the United States of America 2010, 107(52):22487-22492. 10.1073/pnas.1014958107.
76. Guo C., Yoon H.S., Franklin A., Jain S., Ebert A., Cheng H.L., et al. CTCF-binding elements mediate control of V(D)J recombination. Nature 2011, 477(7365):424-430. 10.1038/nature10495.
77. Helmink B.A., Sleckman B.P. The response to and repair of RAG-mediated DNA double-strand breaks. Annual Review of Immunology 2012, 30:175-202. 10.1146/annurev-immunol-030409-101320.
78. Hesse J.E., Lieber M.R., Mizuuchi K., Gellert M. V(D)J recombination: A functional definition of the joining signals. Genes and Development 1989, 3(7):1053-1061.
79. Hesslein D.G., Schatz D.G. Factors and forces controlling V(D)J recombination. Advances in Immunology 2001, 78:169-232.
80. Hewitt S.L., Yin B., Ji Y., Chaumeil J., Marszalek K., Tenthorey J., et al. RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nature Immunology 2009, 10(6):655-664. 10.1038/ni.1735.
81. Hickman A.B., Ewis H.E., Li X., Knapp J.A., Laver T., Doss A.L., et al. Structural basis of hAT transposon end recognition by Hermes, an octameric DNA transposase from Musca domestica. Cell 2014, 158(2):353-367. 10.1016/j.cell.2014.05.037.
82. Hiom K., Gellert M. Assembly of a 12/23 paired signal complex: A critical control point in V(D)J recombination. Molecular Cell 1998, 1(7):1011-1019.
83. Hiom K., Melek M., Gellert M. DNA transposition by the RAG1 and RAG2 proteins: A possible source of oncogenic translocations. Cell 1998, 94(4):463-470.
84. Horowitz J.E., Bassing C.H. Noncore RAG1 regions promote Vbeta rearrangements and alphabeta T cell development by overcoming inherent inefficiency of Vbeta recombination signal sequences. Journal of Immunology 2014, 192(4):1609-1619. 10.4049/jimmunol.1301599.
85. Hu J., Tepsuporn S., Meyers R.M., Gostissa M., Alt F.W. Developmental propagation of V(D)J recombination-associated DNA breaks and translocations in mature B cells via dicentric chromosomes. Proceedings of the National Academy of Sciences of the United States of America 2014, 111(28):10269-10274. 10.1073/pnas.1410112111.
86. Huang S., Chen Z., Yan X., Yu T., Huang G., Yan Q., et al. Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes. Nature Communications 2014, 5:5896. 10.1038/ncomms6896.
87. Hughes M.M., Tillman R.E., Wehrly T.D., White J.M., Sleckman B.P. The B12/23 restriction is critically dependent on recombination signal nonamer and spacer sequences. Journal of Immunology 2003, 171(12):6604-6610.
88. Huye L.E., Purugganan M.M., Jiang M.M., Roth D.B. 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. Molecular and Cellular Biology 2002, 22(10):3460-3473.
89. Janz S. Myc translocations in B cell and plasma cell neoplasms. DNA Repair (Amst) 2006, 5(9-10):1213-1224. 10.1016/j.dnarep.2006.05.017.
90. Jeannet R., Mastio J., Macias-Garcia A., Oravecz A., Ashworth T., Geimer Le Lay A.S., et al. Oncogenic activation of the Notch1 gene by deletion of its promoter in Ikaros-deficient T-ALL. Blood 2010, 116(25):5443-5454. 10.1182/blood-2010-05-286658.
91. Jhunjhunwala S., van Zelm M.C., Peak M.M., Murre C. Chromatin architecture and the generation of antigen receptor diversity. Cell 2009, 138(3):435-448. 10.1016/j.cell.2009.07.016.
92. Ji Y., Resch W., Corbett E., Yamane A., Casellas R., Schatz D.G. The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell 2010, 141(3):419-431. 10.1016/j.cell.2010.03.010.
93. Jones J.M., Bhattacharyya A., Simkus C., Vallieres B., Veenstra T.D., Zhou M. The RAG1 V(D)J recombinase/ubiquitin ligase promotes ubiquitylation of acetylated, phosphorylated histone 3.3. Immunology Letters 2011, 136(2):156-162. 10.1016/j.imlet.2011.01.005.
94. Jones J.M., Gellert M. Intermediates in V(D)J recombination: A stable RAG1/2 complex sequesters cleaved RSS ends. Proceedings of the National Academy of Sciences of the United States of America 2001, 98(23):12926-12931. 10.1073/pnas.221471198.
95. Jones J.M., Gellert M. Autoubiquitylation of the V(D)J recombinase protein RAG1. Proceedings of the National Academy of Sciences of the United States of America 2003, 100(26):15446-15451. 10.1073/pnas.2637012100.
96. Jursch T., Miskey C., Izsvak Z., Ivics Z. Regulation of DNA transposition by CpG methylation and chromatin structure in human cells. Mobile DNA 2013, 4(1):15. 10.1186/1759-8753-4-15.
97. Kapitonov V.V., Jurka J. RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS Biology 2005, 3(6):e181. 10.1371/journal.pbio.0030181.
98. Kapitonov V.V., Koonin E.V. Evolution of the RAG1-RAG2 locus: Both proteins came from the same transposon. Biology Direct 2015, 10(1):20. 10.1186/s13062-015-0055-8.
99. Karo J.M., Schatz D.G., Sun J.C. The RAG recombinase dictates functional heterogeneity and cellular fitness in natural killer cells. Cell 2014, 159(1):94-107. 10.1016/j.cell.2014.08.026.
100. Kassmeier M.D., Mondal K., Palmer V.L., Raval P., Kumar S., Perry G.A., et al. VprBP binds full-length RAG1 and is required for B-cell development and V(D)J recombination fidelity. The EMBO Journal 2012, 31(4):945-958. 10.1038/emboj.2011.455.
101. Kim D.R., Dai Y., Mundy C.L., Yang W., Oettinger M.A. Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase. Genes and Development 1999, 13(23):3070-3080.
102. Kim M.S., Lapkouski M., Yang W., Gellert M. Crystal structure of the V(D)J recombinase RAG1-RAG2. Nature 2015, 518(7540):507-511. 10.1038/nature14174.
103. Klein I.A., Resch W., Jankovic M., Oliveira T., Yamane A., Nakahashi H., et al. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 2011, 147(1):95-106. 10.1016/j.cell.2011.07.048.
104. Kondilis-Mangum H.D., Cobb R.M., Osipovich O., Srivatsan S., Oltz E.M., Krangel M.S. Transcription-dependent mobilization of nucleosomes at accessible TCR gene segments in vivo. Journal of Immunology 2010, 184(12):6970-6977. 10.4049/jimmunol.0903923.
105. Kosak S.T., Skok J.A., Medina K.L., Riblet R., Le Beau M.M., Fisher A.G., et al. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 2002, 296(5565):158-162. 10.1126/science.1068768.
106. Krangel M.S. T cell development: Better living through chromatin. Nature Immunology 2007, 8(7):687-694. 10.1038/ni1484.
107. Kwon J., Imbalzano A.N., Matthews A., Oettinger M.A. Accessibility of nucleosomal DNA to V(D)J cleavage is modulated by RSS positioning and HMG1. Molecular Cell 1998, 2(6):829-839.
108. Landree M.A., Wibbenmeyer J.A., Roth D.B. Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination. Genes and Development 1999, 13(23):3059-3069.
109. Larmonie N.S., Dik W.A., Meijerink J.P., Homminga I., van Dongen J.J., Langerak A.W. Breakpoint sites disclose the role of the V(D)J recombination machinery in the formation of T-cell receptor (TCR) and non-TCR associated aberrations in T-cell acute lymphoblastic leukemia. Haematologica 2013, 98(8):1173-1184. 10.3324/haematol.2012.082156.
110. Leduc F., Faucher D., Bikond Nkoma G., Gregoire M.C., Arguin M., Wellinger R.J., et al. Genome-wide mapping of DNA strand breaks. PloS One 2011, 6(2):e17353. 10.1371/journal.pone.0017353.
111. Lee A.I., Fugmann S.D., Cowell L.G., Ptaszek L.M., Kelsoe G., Schatz D.G. A functional analysis of the spacer of V(D)J recombination signal sequences. PLoS Biology 2003, 1(1):E1. 10.1371/journal.pbio.0000001.
112. Lee G.S., Neiditch M.B., Salus S.S., Roth D.B. RAG proteins shepherd double-strand breaks to a specific pathway, suppressing error-prone repair, but RAG nicking initiates homologous recombination. Cell 2004, 117(2):171-184.
113. Lewis S.M. The mechanism of V(D)J joining: Lessons from molecular, immunological, and comparative analyses. Advances in Immunology 1994, 56:27-150.
114. Lewis S.M., Agard E., Suh S., Czyzyk L. Cryptic signals and the fidelity of V(D)J joining. Molecular and Cellular Biology 1997, 17(6):3125-3136.
115. Li Z., Dordai D.I., Lee J., Desiderio S. A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle. Immunity 1996, 5(6):575-589.
116. Lin S.G., Guo C., Su A., Zhang Y., Alt F.W. CTCF-binding elements 1 and 2 in the Igh intergenic control region cooperatively regulate V(D)J recombination. Proceedings of the National Academy of Sciences of the United States of America 2015, 112(6):1815-1820. 10.1073/pnas.1424936112.
117. Liu Y., Subrahmanyam R., Chakraborty T., Sen R., Desiderio S. 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. 10.1016/j.immuni.2007.09.005.
118. Lovely G.A., Brewster R.C., Schatz D.G., Baltimore D., Phillips R. Single-molecule analysis of RAG-mediated V(D)J DNA cleavage. Proceedings of the National Academy of Sciences of the United States of America 2015, 112(14):E1715-E1723. 10.1073/pnas.1503477112.
119. Lu C., Ward A., Bettridge J., Liu Y., Desiderio S. An autoregulatory mechanism imposes allosteric control on the V(D)J recombinase by histone H3 methylation. Cell Reports 2015, 10(1):29-38. 10.1016/j.celrep.2014.12.001.
120. Lucas J.S., Zhang Y., Dudko O.K., Murre C. 3D trajectories adopted by coding and regulatory DNA elements: First-passage times for genomic interactions. Cell 2014, 158(2):339-352. 10.1016/j.cell.2014.05.036.
121. Marculescu R., Le T., Simon P., Jaeger U., Nadel B. V(D)J-mediated translocations in lymphoid neoplasms: A functional assessment of genomic instability by cryptic sites. The Journal of Experimental Medicine 2002, 195(1):85-98.
122. Matthews A.G., Kuo A.J., Ramon-Maiques S., Han S., Champagne K.S., Ivanov D., et al. RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature 2007, 450(7172):1106-1110. 10.1038/nature06431.
123. McMahan C.J., Difilippantonio M.J., Rao N., Spanopoulou E., Schatz D.G. A basic motif in the N-terminal region of RAG1 enhances V(D)J recombination activity. Molecular and Cellular Biology 1997, 17(8):4544-4552.
124. Medvedovic J., Ebert A., Tagoh H., Tamir I.M., Schwickert T.A., Novatchkova M., et al. Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire. Immunity 2013, 39(2):229-244. 10.1016/j.immuni.2013.08.011.
125. Mizuta R., Mizuta M., Araki S., Kitamura D. RAG2 is down-regulated by cytoplasmic sequestration and ubiquitin-dependent degradation. The Journal of Biological Chemistry 2002, 277(44):41423-41427. 10.1074/jbc.M206605200.
126. Mo X., Bailin T., Sadofsky M.J. RAG1 and RAG2 cooperate in specific binding to the recombination signal sequence in vitro. The Journal of Biological Chemistry 1999, 274(11):7025-7031.
127. Mo X., Bailin T., Sadofsky M.J. A C-terminal region of RAG1 contacts the coding DNA during V(D)J recombination. Molecular and Cellular Biology 2001, 21(6):2038-2047. 10.1128/MCB.21.6.2038-2047.2001.
128. Mombaerts P., Iacomini J., Johnson R.S., Herrup K., Tonegawa S., Papaioannou V.E. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 1992, 68(5):869-877.
129. Nambiar M., Raghavan S.C. Mechanism of fragility at BCL2 gene minor breakpoint cluster region during t(14;18) chromosomal translocation. The Journal of Biological Chemistry 2012, 287(12):8688-8701. 10.1074/jbc.M111.307363.
130. Neiditch M.B., Lee G.S., Huye L.E., Brandt V.L., Roth D.B. The V(D)J recombinase efficiently cleaves and transposes signal joints. Molecular Cell 2002, 9(4):871-878.
131. Nishana M., Raghavan S.C. A non-B DNA can replace heptamer of V(D)J recombination when present along with a nonamer: Implications in chromosomal translocations and cancer. The Biochemical Journal 2012, 448(1):115-125. 10.1042/BJ20121031.
132. Olaru A., Patterson D.N., Cai H., Livak F. Recombination signal sequence variations and the mechanism of patterned T-cell receptor-beta locus rearrangement. Molecular Immunology 2004, 40(16):1189-1201.
133. Onozawa M., Aplan P.D. Illegitimate V(D)J recombination involving nonantigen receptor loci in lymphoid malignancy. Genes, Chromosomes & Cancer 2012, 51(6):525-535. 10.1002/gcc.21942.
134. Papaemmanuil E., Rapado I., Li Y., Potter N.E., Wedge D.C., Tubio J., et al. RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia. Nature Genetics 2014, 46(2):116-125. 10.1038/ng.2874.
135. Pavlicek J.W., Lyubchenko Y.L., Chang Y. Quantitative analyses of RAG-RSS interactions and conformations revealed by atomic force microscopy. Biochemistry 2008, 47(43):11204-11211. 10.1021/bi801426x.
136. Peak M.M., Arbuckle J.L., Rodgers K.K. The central domain of core RAG1 preferentially recognizes single-stranded recombination signal sequence heptamer. The Journal of Biological Chemistry 2003, 278(20):18235-18240. 10.1074/jbc.M302041200.
137. Pilbeam K., Basse P., Brossay L., Vujanovic N., Gerstein R., Vallejo A.N., et al. The ontogeny and fate of NK cells marked by permanent DNA rearrangements. Journal of Immunology 2008, 180(3):1432-1441.
138. Raghavan S.C., Kirsch I.R., Lieber M.R. Analysis of the V(D)J recombination efficiency at lymphoid chromosomal translocation breakpoints. The Journal of Biological Chemistry 2001, 276(31):29126-29133. 10.1074/jbc.M103797200.
139. Raghavan S.C., Swanson P.C., Wu X., Hsieh C.L., Lieber M.R. A non-B-DNA structure at the Bcl-2 major breakpoint region is cleaved by the RAG complex. Nature 2004, 428(6978):88-93. 10.1038/nature02355.
140. Ramon-Maiques S., Kuo A.J., Carney D., Matthews A.G., Oettinger M.A., Gozani O., et al. The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2. Proceedings of the National Academy of Sciences of the United States of America 2007, 104(48):18993-18998. 10.1073/pnas.0709170104.
141. Ramsden D.A., Baetz K., Wu G.E. Conservation of sequence in recombination signal sequence spacers. Nucleic Acids Research 1994, 22(10):1785-1796.
142. Ramsden D.A., Weed B.D., Reddy Y.V. V(D)J recombination: Born to be wild. Seminars in Cancer Biology 2010, 20(4):254-260. 10.1016/j.semcancer.2010.06.002.
143. Ranganath S., Carpenter A.C., Gleason M., Shaw A.C., Bassing C.H., Alt F.W. Productive coupling of accessible Vbeta14 segments and DJbeta complexes determines the frequency of Vbeta14 rearrangement. Journal of Immunology 2008, 180(4):2339-2346.
144. Reddy K.L., Zullo J.M., Bertolino E., Singh H. Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 2008, 452(7184):243-247. 10.1038/nature06727.
145. Rodgers W., Byrum J.N., Sapkota H., Rahman N.S., Cail R.C., Zhao S., et al. Spatio-temporal regulation of RAG2 following genotoxic stress. DNA Repair (Amsterdam) 2015, 27:19-27. 10.1016/j.dnarep.2014.12.008.
146. Rooney S., Chaudhuri J., Alt F.W. The role of the non-homologous end-joining pathway in lymphocyte development. Immunological Reviews 2004, 200:115-131. 10.1111/j.0105-2896.2004.00165.x.
147. Ross A.E., Vuica M., Desiderio S. Overlapping signals for protein degradation and nuclear localization define a role for intrinsic RAG-2 nuclear uptake in dividing cells. Molecular and Cellular Biology 2003, 23(15):5308-5319.
148. Ruthenburg A.J., Allis C.D., Wysocka J. Methylation of lysine 4 on histone H3: Intricacy of writing and reading a single epigenetic mark. Molecular Cell 2007, 25(1):15-30. 10.1016/j.molcel.2006.12.014.
149. Sadofsky M.J., Hesse J.E., Gellert M. Definition of a core region of RAG-2 that is functional in V(D)J recombination. Nucleic Acids Research 1994, 22(10):1805-1809.
150. Sakata J., Inoue J., Ohi H., Kosugi-Okano H., Mishima Y., Hatakeyama K., et al. Involvement of V(D)J recombinase in the generation of intragenic deletions in the Rit1/Bcl11b tumor suppressor gene in gamma-ray-induced thymic lymphomas and in normal thymus of the mouse. Carcinogenesis 2004, 25(6):1069-1075. 10.1093/carcin/bgh094.
151. Schatz D.G. Antigen receptor genes and the evolution of a recombinase. Seminars in Immunology 2004, 16(4):245-256. 10.1016/j.smim.2004.08.004.
152. Schatz D.G., Ji Y. Recombination centres and the orchestration of V(D)J recombination. Nature Reviews. Immunology 2011, 11(4):251-263. 10.1038/nri2941.
153. Schatz D.G., Swanson P.C. V(D)J recombination: Mechanisms of initiation. Annual Review of Genetics 2011, 45:167-202. 10.1146/annurev-genet-110410-132552.
154. Shih H.Y., Krangel M.S. Chromatin architecture, CCCTC-binding factor, and V(D)J recombination: Managing long-distance relationships at antigen receptor loci. Journal of Immunology 2013, 190(10):4915-4921. 10.4049/jimmunol.1300218.
155. Shiloh Y., Ziv Y. The ATM protein kinase: Regulating the cellular response to genotoxic stress, and more. Nature Reviews. Molecular Cell Biology 2013, 14(4):197-210.
156. Shimazaki N., Tsai A.G., Lieber M.R. H3K4me3 stimulates the V(D)J RAG complex for both nicking and hairpinning in trans in addition to tethering in cis: Implications for translocations. Molecular Cell 2009, 34(5):535-544. 10.1016/j.molcel.2009.05.011.
157. Shinkai Y., Rathbun G., Lam K.P., Oltz E.M., Stewart V., Mendelsohn M., et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 1992, 68(5):855-867.
158. Shlyakhtenko L.S., Gilmore J., Kriatchko A.N., Kumar S., Swanson P.C., Lyubchenko Y.L. Molecular mechanism underlying RAG1/RAG2 synaptic complex formation. The Journal of Biological Chemistry 2009, 284(31):20956-20965. 10.1074/jbc.M109.028977.
159. Simkus C., Makiya M., Jones J.M. Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin ligase. Molecular Immunology 2009, 46(7):1319-1325. 10.1016/j.molimm.2008.11.009.
160. Sollbach A.E., Wu G.E. Inversions produced during V(D)J rearrangement at IgH, the immunoglobulin heavy-chain locus. Molecular and Cellular Biology 1995, 15(2):671-681.
161. Steinel N.C., Lee B.S., Tubbs A.T., Bednarski J.J., Schulte E., Yang-Iott K.S., et al. The ataxia telangiectasia mutated kinase controls Igkappa allelic exclusion by inhibiting secondary Vkappa-to-Jkappa rearrangements. The Journal of Experimental Medicine 2013, 210(2):233-239. 10.1084/jem.20121605.
162. Subrahmanyam R., Du H., Ivanova I., Chakraborty T., Ji Y., Zhang Y., et al. Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions. Nature Immunology 2012, 13(12):1205-1212. 10.1038/ni.2447.
163. Swaminathan S., Klemm L., Park E., Papaemmanuil E., Ford A., Kweon S.M., et al. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nature Immunology 2015, 16:766-774.
164. Swanson P.C. The bounty of RAGs: Recombination signal complexes and reaction outcomes. Immunological Reviews 2004, 200:90-114. 10.1111/j.0105-2896.2004.00159.x.
165. Swanson P.C., Desiderio S. RAG-2 promotes heptamer occupancy by RAG-1 in the assembly of a V(D)J initiation complex. Molecular and Cellular Biology 1999, 19(5):3674-3683.
166. Swanson P.C., Kumar S., Raval P. Early steps of V(D)J rearrangement: Insights from biochemical studies of RAG-RSS complexes. Advances in Experimental Medicine and Biology 2009, 650:1-15.
167. Teng G., Maman Y., Resch W., Kim M., Yamane A., Qian J., et al. RAG represents a widespread threat to the lymphocyte genome. Cell 2015, (in press).
168. Tepsuporn S., Hu J., Gostissa M., Alt F.W. Mechanisms that can promote peripheral B-cell lymphoma in ATM-deficient mice. Cancer Immun. Res 2014, 2(9):857-866. 10.1158/2326-6066.CIR-14-0090.
169. Thompson C.B. New insights into V(D)J recombination and its role in the evolution of the immune system. Immunity 1995, 3(5):531-539.
170. Tsai A.G., Lu H., Raghavan S.C., Muschen M., Hsieh C.L., Lieber M.R. Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity. Cell 2008, 135(6):1130-1142. 10.1016/j.cell.2008.10.035.
171. Tsai C.L., Schatz D.G. Regulation of RAG1/RAG2-mediated transposition by GTP and the C-terminal region of RAG2. The EMBO Journal 2003, 22(8):1922-1930. 10.1093/emboj/cdg185.
172. Tsuji H., Ishii-Ohba H., Noda Y., Kubo E., Furuse T., Tatsumi K. Rag-dependent and Rag-independent mechanisms of Notch1 rearrangement in thymic lymphomas of Atm(-/-) and scid mice. Mutation Research 2009, 660(1-2):22-32. 10.1016/j.mrfmmm.2008.10.002.
173. Um J.H., Brown A.L., Singh S.K., Chen Y., Gucek M., Lee B.S., et al. Metabolic sensor AMPK directly phosphorylates RAG1 protein and regulates V(D)J recombination. Proceedings of the National Academy of Sciences of the United States of America 2013, 110(24):9873-9878. 10.1073/pnas.1307928110.
174. Vanura K., Montpellier B., Le T., Spicuglia S., Navarro J.M., Cabaud O., et al. In vivo reinsertion of excised episomes by the V(D)J recombinase: A potential threat to genomic stability. PLoS Biology 2007, 5(3):e43. 10.1371/journal.pbio.0050043.
175. Wang J.H., Gostissa M., Yan C.T., Goff P., Hickernell T., Hansen E., et al. Mechanisms promoting translocations in editing and switching peripheral B cells. Nature 2009, 460(7252):231-236. 10.1038/nature08159.
176. Wang X., Xiao G., Zhang Y., Wen X., Gao X., Okada S., et al. Regulation of Tcrb recombination ordering by c-Fos-dependent RAG deposition. Nature Immunology 2008, 9(7):794-801. 10.1038/ni.1614.
177. West K.L., Singha N.C., De Ioannes P., Lacomis L., Erdjument-Bromage H., Tempst 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. 10.1016/j.immuni.2005.07.004.
178. Wilson A., Held W., MacDonald H.R. Two waves of recombinase gene expression in developing thymocytes. The Journal of Experimental Medicine 1994, 179(4):1355-1360.
179. Wilson D.R., Norton D.D., Fugmann S.D. The PHD domain of the sea urchin RAG2 homolog, SpRAG2L, recognizes dimethylated lysine 4 in histone H3 tails. Developmental and Comparative Immunology 2008, 32(10):1221-1230. 10.1016/j.dci.2008.03.012.
180. Wu C., Ranganath S., Gleason M., Woodman B.B., Borjeson T.M., Alt F.W., et al. Restriction of endogenous T cell antigen receptor beta rearrangements to Vbeta14 through selective recombination signal sequence modifications. Proceedings of the National Academy of Sciences of the United States of America 2007, 104(10):4002-4007. 10.1073/pnas.0700081104.
181. Yant S.R., Wu X., Huang Y., Garrison B., Burgess S.M., Kay M.A. High-resolution genome-wide mapping of transposon integration in mammals. Molecular and Cellular Biology 2005, 25(6):2085-2094. 10.1128/MCB.25.6.2085-2094.2005.
182. Yin F.F., Bailey S., Innis C.A., Ciubotaru M., Kamtekar S., Steitz T.A., et al. Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis. Nature Structural & Molecular Biology 2009, 16(5):499-508. 10.1038/nsmb.1593.
183. Yu K., Taghva A., Lieber M.R. The cleavage efficiency of the human immunoglobulin heavy chain VH elements by the RAG complex: Implications for the immune repertoire. The Journal of Biological Chemistry 2002, 277(7):5040-5046. 10.1074/jbc.M109772200.
184. Yurchenko V., Xue Z., Sadofsky M. The RAG1 N-terminal domain is an E3 ubiquitin ligase. Genes and Development 2003, 17(5):581-585. 10.1101/gad.1058103.
185. Zhang Z., Espinoza C.R., Yu Z., Stephan R., He T., Williams G.S., et al. Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes. Nature Immunology 2006, 7(6):616-624. 10.1038/ni1339.
186. Zhang Y., McCord R.P., Ho Y.J., Lajoie B.R., Hildebrand D.G., Simon A.C., et al. Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell 2012, 148(5):908-921. 10.1016/j.cell.2012.02.002.
187. Zhang L., Reynolds T.L., Shan X., Desiderio S. Coupling of V(D)J recombination to the cell cycle suppresses genomic instability and lymphoid tumorigenesis. Immunity 2011, 34(2):163-174. 10.1016/j.immuni.2011.02.003.
188. Zhang Y.H., Shetty K., Surleac M.D., Petrescu A.J., Schatz D.G. Mapping and quantitation of the interaction between the recombination activating gene proteins RAG1 and RAG2. The Journal of Biological Chemistry 2015, 290(19):11802-11817. 10.1074/jbc.M115.638627.
189. Zhang M., Swanson P.C. V(D)J recombinase binding and cleavage of cryptic recombination signal sequences identified from lymphoid malignancies. The Journal of Biological Chemistry 2008, 283(11):6717-6727. 10.1074/jbc.M710301200.
190. Zhang Y., Xu K., Deng A., Fu X., Xu A., Liu X. An amphioxus RAG1-like DNA fragment encodes a functional central domain of vertebrate core RAG1. Proceedings of the National Academy of Sciences of the United States of America 2014, 111(1):397-402. 10.1073/pnas.1318843111.
191. Zhu C., Mills K.D., Ferguson D.O., Lee C., Manis J., Fleming J., et al. Unrepaired DNA breaks in p53-deficient cells lead to oncogenic gene amplification subsequent to translocations. Cell 2002, 109(7):811-821.