Antibody Diversity; Antibody Formation; Biological Evolution; Genes, Immunoglobulin; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Molecular Biology; Gene Rearrangement, B-Lymphocyte; Gene Rearrangement, T-Lymphocyte; Developmental Biology; Somatic Hypermutation, Immunoglobulin
Discovery to Cure Internship
Rheumatic Diseases Research Core
Generating a Diverse and Effective Repertoire of Antibodies During an Immune Response:
The Schatz laboratory studies V(D)J recombination and somatic hypermutation, reactions that create and optimize antibody genes. Antibodies are blood proteins produced by B cells that are important for fighting infectious disease. V(D)J recombination puts antibody genes together from small pieces of chromosomal DNA, while somatic hypermutation makes mutations in antibody genes and allows for the generation of antibodies that bind viruses and bacteria very tightly. We study these reactions using a wide variety of molecular, genetic, cellular, and biochemical approaches. The focus of our research is understanding the underlying mechanisms of these reactions and how they are targeted specifically to antibody genes. We are also interested in understanding why V(D)J recombination and somatic hypermutation sometimes affect the wrong genes, and how such mistakes contribute to the development of B cell cancers known as lymphomas and leukemias. Finally, we are interested in the evolutionary origins of V(D)J recombination, and study transposons that are thought to be evolutionary relatives of RAG1 and RAG2.
Extensive Research Description
Generating a Diverse and Effective Repertoire of Antigen-Specific Receptors During Development of the Immune System
The B and T lymphocytes that constitute the adaptive immune system make use of antigen receptor molecules, known as immunoglobulins and T cell receptors, to combat viral and bacterial infections. Each of the hundreds of millions of lymphocytes expresses a different antigen receptor on its surface, indicative of an extraordinary level of diversity in these receptors. The fundamental interest of our lab is to understand the two major processes that generate this diversity: V(D)J recombination and somatic hypermutation.
V(D)J recombination assembles immunoglobulin and T cell receptor genes from component V (variable), D (diversity), and J (joining) gene segments in developing B and T cells. In the first phase of the reaction, two DNA segments are bound by the recombination machinery, brought into close physical proximity, and the DNA is cleaved. In the second phase, the DNA ends are processed and joined by the cellular DNA repair machinery to form the reaction products.
One of our major interests is the enzymatic mechanism of the first phase of V(D)J recombination, which is catalyzed by the proteins encoded by the recombination-activating genes, RAG1 and RAG2. We are studying how the RAG proteins bend and twist the substrate DNA during DNA cleavage and are using a variety of ensemble and single molecule biophysical assays to characterize the structure, composition, and stability of the DNA complexes formed by RAG1/RAG2.
We have used chromatin immunoprecipitation (ChIP) to demonstrate that the RAG proteins associate with one small, discrete region of each antigen receptor locus. These regions, which we refer to as recombination centers, are rich in activating histone modifications and RNA polymerase II. We propose that recombination centers are specialized sites within which the RAG proteins bind one DNA segment and then capture a second to allow for recombination. We have also demonstrated that RAG1 and RAG2 bind to thousands of other sites in the genome, almost entirely at active promoters and enhancers. Computational analysis suggests that RAG binding is driven by interactions with chromatin proteins including modified histone tails, and that this is mediated by regulatory regions in both RAG1 and RAG2. We are now working to understand the molecular interactions that mediate RAG binding patterns and the implications of wide-spread RAG binding for genome stability in developing lymphocytes.
We have a long standing interest in the evolutionary origins of RAG1 and RAG2, beginning with our demonstration in 1998 that these proteins possess cut-and-paste DNA transposase activity. We are studying evolutionarily related transposases such as Transib and ProtoRAG, with the hope of understanding the steps that led to evolution of our adaptive immune system.
Somatic hypermutation (SHM) introduces point mutations into the variable regions of immunoglobulin genes in B cells during an immune response. These mutations allow for the generation of B cells expressing antibodies with high affinity for an invading microorganism, a process known as affinity maturation. This process is important for the "memory" of the immune system, which helps protect individuals from recurrent infections with the same microorganism, and underlies the success of many vaccines.
SHM is initiated by an enzyme known as activation-induced deaminase (AID), which deaminates cytosine to create uracil in immunoglobulin genes. The uracil is then processed by the mismatch and base excision repair pathways to create mutations at the site of deamination and at nearby sites in the DNA. SHM has been linked to genomic instability and B cell cancers, and our lab is interested in understanding how the reaction is targeted to immunoglobulin loci and how the rest of the genome is protected from its deleterious effects. We have demonstrated that immunoglobulin enhancer elements function as SHM targeting elements (which we refer to as DIVAC--diversification activator) and are very likely responsible for the high efficiency with which immunoglobulin genes undergo SHM. We are now studying the protein factors that bind to DIVAC and attempting to understand the mechanism by which they enhance SHM. In addition, we have developed methods for scanning the human genome for regions that intrinsically sensitive or resistant to AID/SHM and are working experimentally and computationally to determine the rules that dictate susceptibility to AID/SHM.
Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination
Huang, S., Tao, X., Yuan, S., Zhang, Y., Li, P., Beilinson, H.A., Zhang, Y., Yu, W., Pontarotti, P., Escriva, H., Le Petillon, Y., Liu, X., Chen, S., Schatz, D.G., and Xu, A. (2016). Cell 166, 102-114.
Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination
Carmona, L.M., Fugmann, S.D., and Schatz, D.G. (2016). Genes Dev 30, 909-917.
RAG Represents a Widespread Threat to the Lymphocyte Genome.
Teng, G., Maman, Y., Resch, W., Kim, M., Yamane, A., Qian, J., Kieffer-Kwon, K.R., Mandal, M., Ji, Y., Meffre, E., Clark, M.R., Cowell, L.G., Casellas, R., and Schatz, D.G. (2015). Cell 162, 751-765.
Targeting of somatic hypermutation by immunoglobulin enhancer and enhancer-like sequences.
Buerstedde, J.M., Alinikula, J., Arakawa, H., McDonald, J.J., and Schatz, D.G. (2014). Targeting of somatic hypermutation by immunoglobulin enhancer and enhancer-like sequences. PLoS Biol 12, e1001831.
The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci
Ji, Y., Resch, W., Corbett, E., Yamane, A., Casellas, R., and Schatz, D.G. (2010). The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell 141, 419-431.
Two levels of protection for the B cell genome during somatic hypermutation.
Liu, M., Duke, J. L., Richter, D. J., Vinuesa, C. G., Goodnow, C. C., Kleinstein, S. H. and Schatz, D. G. Two levels of protection for the B cell genome during somatic hypermutation. Nature 451, 841-845 (2008)
Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination
Carmona, L.M., Fugmann, S.D., and Schatz, D.G. (2016) Genes Dev. 30, 909-917
Full List of PubMed Publications
- Carmona LM, Schatz DG: New insights into the evolutionary origins of the recombination-activating gene proteins and V(D)J recombination. FEBS J. 2017 Jun; 2017 Jan 6. PMID: 27973733
- Fisher MR, Rivera-Reyes A, Bloch NB, Schatz DG, Bassing CH: Immature Lymphocytes Inhibit Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double-Strand Breaks. J Immunol. 2017 Apr 1; 2017 Feb 17. PMID: 28213501
- Maman Y, Teng G, Seth R, Kleinstein SH, Schatz DG: RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2. Nucleic Acids Res. 2016 Nov 16; 2016 Jul 19. PMID: 27436288
- Brauer PM, Pessach IM, Clarke E, Rowe JH, Ott de Bruin L, Lee YN, Dominguez-Brauer C, Comeau AM, Awong G, Felgentreff K, Zhang YH, Bredemeyer A, Al-Herz W, Du L, Ververs F, Kennedy M, Giliani S, Keller G, Sleckman BP, Schatz DG, Bushman FD, Notarangelo LD, Zúñiga-Pflücker JC: Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies. Blood. 2016 Aug 11; 2016 Jun 14. PMID: 27301863
- Huang S, Tao X, Yuan S, Zhang Y, Li P, Beilinson HA, Zhang Y, Yu W, Pontarotti P, Escriva H, Le Petillon Y, Liu X, Chen S, Schatz DG, Xu A: Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination. Cell. 2016 Jun 30; 2016 Jun 9. PMID: 27293192
- Carmona LM, Fugmann SD, Schatz DG: Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination. Genes Dev. 2016 Apr 15; 2016 Apr 7. PMID: 27056670
- Williams AM, Maman Y, Alinikula J, Schatz DG: Bcl6 Is Required for Somatic Hypermutation and Gene Conversion in Chicken DT40 Cells. PLoS One. 2016; 2016 Feb 22. PMID: 26900682
- Hu J, Zhang Y, Zhao L, Frock RL, Du Z, Meyers RM, Meng FL, Schatz DG, Alt FW: Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes. Cell. 2015 Nov 5; 2015 Oct 22. PMID: 26593423
- Shetty K, Schatz DG: Recruitment of RAG1 and RAG2 to Chromatinized DNA during V(D)J Recombination. Mol Cell Biol. 2015 Nov; 2015 Aug 24. PMID: 26303526
- Mandal M, Hamel KM, Maienschein-Cline M, Tanaka A, Teng G, Tuteja JH, Bunker JJ, Bahroos N, Eppig JJ, Schatz DG, Clark MR: Histone reader BRWD1 targets and restricts recombination to the Igk locus. Nat Immunol. 2015 Oct; 2015 Aug 24. PMID: 26301565
- Choi J, Goh G, Walradt T, Hong BS, Bunick CG, Chen K, Bjornson RD, Maman Y, Wang T, Tordoff J, Carlson K, Overton JD, Liu KJ, Lewis JM, Devine L, Barbarotta L, Foss FM, Subtil A, Vonderheid EC, Edelson RL, Schatz DG, Boggon TJ, Girardi M, Lifton RP: Genomic landscape of cutaneous T cell lymphoma. Nat Genet. 2015 Sep; 2015 Jul 20. PMID: 26192916
- Teng G, Maman Y, Resch W, Kim M, Yamane A, Qian J, Kieffer-Kwon KR, Mandal M, Ji Y, Meffre E, Clark MR, Cowell LG, Casellas R, Schatz DG: RAG Represents a Widespread Threat to the Lymphocyte Genome. Cell. 2015 Aug 13; 2015 Jul 30. PMID: 26234156
- Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon SM, Trageser D, Hasselfeld B, Henke N, Mooster J, Geng H, Schwarz K, Kogan SC, Casellas R, Schatz DG, Lieber MR, Greaves MF, Müschen M: Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nat Immunol. 2015 Jul; 2015 May 18. PMID: 25985233
- Zhang YH, Shetty K, Surleac MD, Petrescu AJ, Schatz DG: Mapping and Quantitation of the Interaction between the Recombination Activating Gene Proteins RAG1 and RAG2. J Biol Chem. 2015 May 8; 2015 Mar 5. PMID: 25745109
- Lovely GA, Brewster RC, Schatz DG, Baltimore D, Phillips R: Single-molecule analysis of RAG-mediated V(D)J DNA cleavage. Proc Natl Acad Sci U S A. 2015 Apr 7; 2015 Mar 23. PMID: 25831509
- Rodgers W, Byrum JN, Sapkota H, Rahman NS, Cail RC, Zhao S, Schatz DG, Rodgers KK: Spatio-temporal regulation of RAG2 following genotoxic stress. DNA Repair (Amst). 2015 Mar; 2015 Jan 8. PMID: 25625798
- Teng G, Schatz DG: Regulation and Evolution of the RAG Recombinase. Adv Immunol. 2015; 2015 Aug 4. PMID: 26477364
- Ciubotaru M, Surleac MD, Metskas LA, Koo P, Rhoades E, Petrescu AJ, Schatz DG: The architecture of the 12RSS in V(D)J recombination signal and synaptic complexes. Nucleic Acids Res. 2015 Jan; 2014 Dec 29. PMID: 25550426
- Alinikula J, Schatz DG: Super-enhancer transcription converges on AID. Cell. 2014 Dec 18. PMID: 25525869
- Karo JM, Schatz DG, Sun JC: The RAG recombinase dictates functional heterogeneity and cellular fitness in natural killer cells. Cell. 2014 Sep 25. PMID: 25259923
- Buerstedde JM, Lowndes N, Schatz DG: Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein. Elife. 2014 Jul 8; 2014 Jul 8. PMID: 25006166
- Banerjee JK, Schatz DG: Synapsis alters RAG-mediated nicking at Tcrb recombination signal sequences: implications for the “beyond 12/23” rule. Mol Cell Biol. 2014 Jul. PMID: 24797073
- Buerstedde JM, Alinikula J, Arakawa H, McDonald JJ, Schatz DG: Targeting of somatic hypermutation by immunoglobulin enhancer and enhancer-like sequences. PLoS Biol. 2014 Apr; 2014 Apr 1. PMID: 24691034
- Chan EA, Teng G, Corbett E, Choudhury KR, Bassing CH, Schatz DG, Krangel MS: Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2. Proc Natl Acad Sci U S A. 2013 Nov 26; 2013 Nov 11. PMID: 24218622
- McDonald JJ, Alinikula J, Buerstedde JM, Schatz DG: A critical context-dependent role for E boxes in the targeting of somatic hypermutation. J Immunol. 2013 Aug 15; 2013 Jul 8. PMID: 23836058
- Duke JL, Liu M, Yaari G, Khalil AM, Tomayko MM, Shlomchik MJ, Schatz DG, Kleinstein SH: Multiple transcription factor binding sites predict AID targeting in non-Ig genes. J Immunol. 2013 Apr 15; 2013 Mar 20. PMID: 23514741
- Little AJ, Corbett E, Ortega F, Schatz DG: Cooperative recruitment of HMGB1 during V(D)J recombination through interactions with RAG1 and DNA. Nucleic Acids Res. 2013 Mar 1; 2013 Jan 15. PMID: 23325855
- Chaumeil J, Micsinai M, Ntziachristos P, Deriano L, Wang JM, Ji Y, Nora EP, Rodesch MJ, Jeddeloh JA, Aifantis I, Kluger Y, Schatz DG, Skok JA: Higher-order looping and nuclear organization of Tcra facilitate targeted rag cleavage and regulated rearrangement in recombination centers. Cell Rep. 2013 Feb 21; 2013 Feb 14. PMID: 23416051
- Steinel NC, Lee BS, Tubbs AT, Bednarski JJ, Schulte E, Yang-Iott KS, Schatz DG, Sleckman BP, Bassing CH: The ataxia telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements. J Exp Med. 2013 Feb 11; 2013 Feb 4. PMID: 23382544
- Ciubotaru M, Trexler AJ, Spiridon LN, Surleac MD, Rhoades E, Petrescu AJ, Schatz DG: RAG and HMGB1 create a large bend in the 23RSS in the V(D)J recombination synaptic complexes. Nucleic Acids Res. 2013 Feb 1; 2013 Jan 4. PMID: 23293004
- Kohler KM, McDonald JJ, Duke JL, Arakawa H, Tan S, Kleinstein SH, Buerstedde JM, Schatz DG: Identification of core DNA elements that target somatic hypermutation. J Immunol. 2012 Dec 1; 2012 Oct 19. PMID: 23087403
- Subrahmanyam R, Du H, Ivanova I, Chakraborty T, Ji Y, Zhang Y, Alt FW, Schatz DG, Sen R: Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions. Nat Immunol. 2012 Dec; 2012 Oct 28. PMID: 23104096
- Coster G, Gold A, Chen D, Schatz DG, Goldberg M: A dual interaction between the DNA damage response protein MDC1 and the RAG1 subunit of the V(D)J recombinase. J Biol Chem. 2012 Oct 19; 2012 Aug 31. PMID: 22942284
- Koduru S, Wong E, Strowig T, Sundaram R, Zhang L, Strout MP, Flavell RA, Schatz DG, Dhodapkar KM, Dhodapkar MV: Dendritic cell-mediated activation-induced cytidine deaminase (AID)-dependent induction of genomic instability in human myeloma. Blood. 2012 Mar 8; 2012 Jan 10. PMID: 22234692
- Gramlich HS, Reisbig T, Schatz DG: AID-targeting and hypermutation of non-immunoglobulin genes does not correlate with proximity to immunoglobulin genes in germinal center B cells. PLoS One. 2012; 2012 Jun 29. PMID: 22768095
- Seitan VC, Hao B, Tachibana-Konwalski K, Lavagnolli T, Mira-Bontenbal H, Brown KE, Teng G, Carroll T, Terry A, Horan K, Marks H, Adams DJ, Schatz DG, Aragon L, Fisher AG, Krangel MS, Nasmyth K, Merkenschlager M: A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation. Nature. 2011 Aug 10; 2011 Aug 10. PMID: 21832993
- Schatz DG, Ji Y: Recombination centres and the orchestration of V(D)J recombination. Nat Rev Immunol. 2011 Apr; 2011 Mar 11. PMID: 21394103
- Schatz DG, Swanson PC: V(D)J recombination: mechanisms of initiation. Annu Rev Genet. 2011; 2011 Aug 19. PMID: 21854230
- Maul RW, Saribasak H, Martomo SA, McClure RL, Yang W, Vaisman A, Gramlich HS, Schatz DG, Woodgate R, Wilson DM 3rd, Gearhart PJ: Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nat Immunol. 2011 Jan; 2010 Dec 12. PMID: 21151102
- Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, Schatz DG: Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. J Exp Med. 2010 Dec 20; 2010 Nov 29. PMID: 21115692
- Lazorchak AS, Liu D, Facchinetti V, Di Lorenzo A, Sessa WC, Schatz DG, Su B: Sin1-mTORC2 suppresses rag and il7r gene expression through Akt2 in B cells. Mol Cell. 2010 Aug 13. PMID: 20705244
- Ji Y, Resch W, Corbett E, Yamane A, Casellas R, Schatz DG: The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor loci. Cell. 2010 Apr 30; 2010 Apr 15. PMID: 20398922
- Strout MP, Schatz DG: Imatinib resistance and progression of CML to blast crisis: somatic hypermutation AIDing the way. Cancer Cell. 2009 Sep 8. PMID: 19732715
- Hewitt SL, Yin B, Ji Y, Chaumeil J, Marszalek K, Tenthorey J, Salvagiotto G, Steinel N, Ramsey LB, Ghysdael J, Farrar MA, Sleckman BP, Schatz DG, Busslinger M, Bassing CH, Skok JA: RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat Immunol. 2009 Jun. PMID: 19448632
- Yin FF, Bailey S, Innis CA, Ciubotaru M, Kamtekar S, Steitz TA, Schatz DG: Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis. Nat Struct Mol Biol. 2009 May; 2009 Apr 26. PMID: 19396172
- Hesslein DG, Fretz JA, Xi Y, Nelson T, Zhou S, Lorenzo JA, Schatz DG, Horowitz MC: Ebf1-dependent control of the osteoblast and adipocyte lineages. Bone. 2009 Apr; 2008 Dec 16. PMID: 19130908
- Liu M, Schatz DG: Balancing AID and DNA repair during somatic hypermutation. Trends Immunol. 2009 Apr; 2009 Mar 18. PMID: 19303358
- Giblin W, Chatterji M, Westfield G, Masud T, Theisen B, Cheng HL, DeVido J, Alt FW, Ferguson DO, Schatz DG, Sekiguchi J: Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation. Blood. 2009 Mar 26; 2009 Jan 6. PMID: 19126872
- Liu M, Duke JL, Richter DJ, Vinuesa CG, Goodnow CC, Kleinstein SH, Schatz DG: Two levels of protection for the B cell genome during somatic hypermutation. Nature. 2008 Feb 14. PMID: 18273020
- Schatz DG, Oettinger MA, Baltimore D: Pillars article: the V(D)J recombination activating gene, RAG-1. 1989. J Immunol. 2008 Jan 1. PMID: 18096996
- Chatterji M, Unniraman S, McBride KM, Schatz DG: Role of activation-induced deaminase protein kinase A phosphorylation sites in Ig gene conversion and somatic hypermutation. J Immunol. 2007 Oct 15. PMID: 17911613
- Drejer-Teel AH, Fugmann SD, Schatz DG: The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Mol Cell Biol. 2007 Sep; 2007 Jul 16. PMID: 17636023
- Yang SY, Fugmann SD, Gramlich HS, Schatz DG: Activation-induced cytidine deaminase-mediated sequence diversification is transiently targeted to newly integrated DNA substrates. J Biol Chem. 2007 Aug 31; 2007 Jul 5. PMID: 17613522
- Unniraman S, Schatz DG: Strand-biased spreading of mutations during somatic hypermutation. Science. 2007 Aug 31. PMID: 17761884
- Ciubotaru M, Kriatchko AN, Swanson PC, Bright FV, Schatz DG: Fluorescence resonance energy transfer analysis of recombination signal sequence configuration in the RAG1/2 synaptic complex. Mol Cell Biol. 2007 Jul; 2007 Apr 30. PMID: 17470556
- Schatz DG: DNA deaminases converge on adaptive immunity. Nat Immunol. 2007 Jun. PMID: 17514205
- Yang SY, Schatz DG: Targeting of AID-mediated sequence diversification by cis-acting determinants. Adv Immunol. 2007. PMID: 17560273
- Yang SY, Fugmann SD, Schatz DG: Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences. J Exp Med. 2006 Dec 25; 2006 Dec 18. PMID: 17178919
- Unniraman S, Schatz DG: AID and Igh switch region-Myc chromosomal translocations. DNA Repair (Amst). 2006 Sep 8; 2006 Jun 19. PMID: 16784901
- Odegard VH, Schatz DG: Targeting of somatic hypermutation. Nat Rev Immunol. 2006 Aug. PMID: 16868548
- Inlay MA, Gao HH, Odegard VH, Lin T, Schatz DG, Xu Y: Roles of the Ig kappa light chain intronic and 3' enhancers in Igk somatic hypermutation. J Immunol. 2006 Jul 15. PMID: 16818772
- Chatterji M, Tsai CL, Schatz DG: Mobilization of RAG-generated signal ends by transposition and insertion in vivo. Mol Cell Biol. 2006 Feb. PMID: 16449665
- Hesslein DG, Yang SY, Schatz DG: Origins of peripheral B cells in IL-7 receptor-deficient mice. Mol Immunol. 2006 Feb. PMID: 16310046
- Horowitz MC, Bothwell AL, Hesslein DG, Pflugh DL, Schatz DG: B cells and osteoblast and osteoclast development. Immunol Rev. 2005 Dec. PMID: 16313346
- Jones KR, Gewirtz DA, Yannone SM, Zhou S, Schatz DG, Valerie K, Povirk LF: Radiosensitization of MDA-MB-231 breast tumor cells by adenovirus-mediated overexpression of a fragment of the XRCC4 protein. Mol Cancer Ther. 2005 Oct. PMID: 16227403
- Rush JS, Liu M, Odegard VH, Unniraman S, Schatz DG: Expression of activation-induced cytidine deaminase is regulated by cell division, providing a mechanistic basis for division-linked class switch recombination. Proc Natl Acad Sci U S A. 2005 Sep 13; 2005 Sep 2. PMID: 16141332
- Odegard VH, Kim ST, Anderson SM, Shlomchik MJ, Schatz DG: Histone modifications associated with somatic hypermutation. Immunity. 2005 Jul. PMID: 16039583
- Horowitz MC, Xi Y, Pflugh DL, Hesslein DG, Schatz DG, Lorenzo JA, Bothwell AL: Pax5-deficient mice exhibit early onset osteopenia with increased osteoclast progenitors. J Immunol. 2004 Dec 1. PMID: 15557148
- Unniraman S, Zhou S, Schatz DG: Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc. Nat Immunol. 2004 Nov; 2004 Oct 17. PMID: 15489857
- Ciubotaru M, Schatz DG: Synapsis of recombination signal sequences located in cis and DNA underwinding in V(D)J recombination. Mol Cell Biol. 2004 Oct. PMID: 15367690
- Unniraman S, Fugmann SD, Schatz DG: Immunology. UNGstoppable switching. Science. 2004 Aug 20. PMID: 15326342
- Chatterji M, Tsai CL, Schatz DG: New concepts in the regulation of an ancient reaction: transposition by RAG1/RAG2. Immunol Rev. 2004 Aug. PMID: 15242411
- Schatz DG: V(D)J recombination. Immunol Rev. 2004 Aug. PMID: 15242391
- Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K: B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5. Nat Immunol. 2004 Aug; 2004 Jul 18. PMID: 15258579
- Schatz DG: Antigen receptor genes and the evolution of a recombinase. Semin Immunol. 2004 Aug. PMID: 15522623
- Repasky JA, Corbett E, Boboila C, Schatz DG: Mutational analysis of terminal deoxynucleotidyltransferase-mediated N-nucleotide addition in V(D)J recombination. J Immunol. 2004 May 1. PMID: 15100289
- Rush JS, Fugmann SD, Schatz DG: Staggered AID-dependent DNA double strand breaks are the predominant DNA lesions targeted to S mu in Ig class switch recombination. Int Immunol. 2004 Apr. PMID: 15039385
- Fugmann SD, Rush JS, Schatz DG: Non-redundancy of cytidine deaminases in class switch recombination. Eur J Immunol. 2004 Mar. PMID: 14991614
- Schatz DG, Baltimore D: Uncovering the V(D)J recombinase. Cell. 2004 Jan 23. PMID: 15055595
- Zheng WP, Zhao Q, Zhao X, Li B, Hubank M, Schatz DG, Flavell RA: Up-regulation of Hlx in immature Th cells induces IFN-gamma expression. J Immunol. 2004 Jan 1. PMID: 14688316
- Hubank M, Bryntesson F, Regan J, Schatz DG: Cloning of apoptosis-related genes by representational difference analysis of cDNA. Methods Mol Biol. 2004. PMID: 15105570
- Shockett PE, Zhou S, Hong X, Schatz DG: Partial reconstitution of V(D)J rearrangement and lymphocyte development in RAG-deficient mice expressing inducible, tetracycline-regulated RAG transgenes. Mol Immunol. 2004 Jan. PMID: 14687938
- Tsai CL, Chatterji M, Schatz DG: DNA mismatches and GC-rich motifs target transposition by the RAG1/RAG2 transposase. Nucleic Acids Res. 2003 Nov 1. PMID: 14576304
- Lee AI, Fugmann SD, Cowell LG, Ptaszek LM, Kelsoe G, Schatz DG: A functional analysis of the spacer of V(D)J recombination signal sequences. PLoS Biol. 2003 Oct; 2003 Oct 13. PMID: 14551903
- Fugmann SD, Schatz DG: RNA AIDS DNA. Nat Immunol. 2003 May. PMID: 12719733
- Tsai CL, Schatz DG: Regulation of RAG1/RAG2-mediated transposition by GTP and the C-terminal region of RAG2. EMBO J. 2003 Apr 15. PMID: 12682024
- Rooney S, Alt FW, Lombard D, Whitlow S, Eckersdorff M, Fleming J, Fugmann S, Ferguson DO, Schatz DG, Sekiguchi J: Defective DNA repair and increased genomic instability in Artemis-deficient murine cells. J Exp Med. 2003 Mar 3. PMID: 12615897
- Ciubotaru M, Ptaszek LM, Baker GA, Baker SN, Bright FV, Schatz DG: RAG1-DNA binding in V(D)J recombination. Specificity and DNA-induced conformational changes revealed by fluorescence and CD spectroscopy. J Biol Chem. 2003 Feb 21; 2002 Dec 17. PMID: 12488446
- Hesslein DG, Pflugh DL, Chowdhury D, Bothwell AL, Sen R, Schatz DG: Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments. Genes Dev. 2003 Jan 1. PMID: 12514097
- Jung D, Bassing CH, Fugmann SD, Cheng HL, Schatz DG, Alt FW: Extrachromosomal recombination substrates recapitulate beyond 12/23 restricted VDJ recombination in nonlymphoid cells. Immunity. 2003 Jan. PMID: 12530976
- Tsai CL, Drejer AH, Schatz DG: Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination. Genes Dev. 2002 Aug 1. PMID: 12154124
- Chen J, Kelz MB, Zeng G, Steffen C, Shockett PE, Terwilliger G, Schatz DG, Nestler EJ: Inducible, reversible hair loss in transgenic mice. Transgenic Res. 2002 Jun. PMID: 12113456
- Papavasiliou FN, Schatz DG: The activation-induced deaminase functions in a postcleavage step of the somatic hypermutation process. J Exp Med. 2002 May 6. PMID: 11994424
- Papavasiliou FN, Schatz DG: Somatic hypermutation of immunoglobulin genes: merging mechanisms for genetic diversity. Cell. 2002 Apr. PMID: 11983151
- Fugmann SD, Schatz DG: Immunology. One AID to unite them all. Science. 2002 Feb 15. PMID: 11847327