Now showing items 1-20 of 21

    • Analysis of Mice Lacking DNaseI Hypersensitive Sites at the 5′ End of the IgH Locus 

      Perlot, Thomas; Pawlitzky, Inka; Manis, John P.; Zarrin, Ali A.; Brodeur, Peter H.; Alt, Frederick W. (Public Library of Science, 2010)
      The 5′ end of the IgH locus contains a cluster of DNaseI hypersensitive sites, one of which (HS1) was shown to be pro-B cell specific and to contain binding sites for the transcription factors PU.1, E2A, and Pax5. These ...
    • ATM-deficient Thymic Lymphoma is Associated with Aberrant tcrd Rearrangement and Gene Amplification 

      Bassing, Craig H.; Brush, James W.; Patel, Harin; Goff, Peter H.; Gatti, Richard A.; Zha, Shan; Sanda, Takaomi; Murphy, Michael M.; Tepsuporn, Suprawee; Look, A. Thomas; Alt, Frederick W. (The Rockefeller University Press, 2010)
      Ataxia telangiectasia mutated (ATM) deficiency predisposes humans and mice to T lineage lymphomas with recurrent chromosome 14 translocations involving the T cell receptor α/δ (Tcra/d) locus. Such translocations have been ...
    • CTCF Orchestrates Long-Range Cohesin-Driven V(D)J Recombinational Scanning 

      Ba, Zhaoqing; Lou, Jiangman; Ye, Adam Yongxin; Dring, Edward; Lin, Sherry G.; Jain, Suvi; Kyritsis, Nia; Kieffer-Kwon, Kyong-Rim; Casellas, Rafael; Alt, Frederick (Springer Nature Publishing Group, 2020-07-27)
      RAG endonuclease initiates V(D)J recombination in progenitor (pro)-B cells1. Upon binding a recombination center (RC)-based JH, RAG scans upstream chromatin via loop extrusion, potentially mediated by cohesin, to locate ...
    • eccDNAs are apoptotic products with high innate immunostimulatory activity 

      Wang, Yuangao; Wang, Meng; Djekidel, Mohamed Nadhir; Chen, Huan; Liu, Di; Alt, Frederick; Zhang, Yi (Springer Science and Business Media LLC, 2021-10-20)
    • Elucidating Mechanisms of IgH Class Switch Recombination Involving Switch Regions and Double Strand Break Joining 

      Zhang, Tingting (2013-02-22)
      During IgH class switch recombination (CSR) in mature B lymphocytes, activation-induced cytidine deaminase (AID) initiates DNA double strand breaks (DSBs) within switch (S) regions flanking different sets of the IgH locus ...
    • Epigenetic Tethering of AID to the Donor Switch Region during Immunoglobulin Class Switch Recombination 

      Jeevan-Raj, Beena Patricia; Robert, Isabelle; Heyer, Vincent; Page, Adeline; Wang, Jing H.; Cammas, Florence; Alt, Frederick W.; Losson, Régine; Reina-San-Martin, Bernardo (The Rockefeller University Press, 2011)
      Immunoglobulin class switch recombination (CSR) is initiated by double-stranded DNA breaks (DSBs) in switch regions triggered by activation-induced cytidine deaminase (AID). Although CSR correlates with epigenetic modifications ...
    • Essential Developmental, Genomic Stability, and Tumour Suppressor Functions of the Mouse Orthologue of hSSB1/NABP2 

      Shi, Wei; Bain, Amanda L.; Schwer, Bjoern; Al-Ejeh, Fares; Smith, Corey; Wong, Lee; Chai, Hua; Miranda, Mariska S.; Ho, Uda; Kawaguchi, Makoto; Miura, Yutaka; Finnie, John W.; Wall, Meaghan; Heierhorst, Jörg; Wicking, Carol; Spring, Kevin J.; Alt, Frederick W.; Khanna, Kum Kum (Public Library of Science, 2013)
      Single-stranded DNA binding proteins (SSBs) regulate multiple DNA transactions, including replication, transcription, and repair. We recently identified SSB1 as a novel protein critical for the initiation of ATM signaling ...
    • Fundamental Roles of Chromatin Loop Extrusion in Antibody Class Switching 

      Zhang, Xuefei; Zhang, Yu; Ba, Zhaoqing; Kyritsis, Nia; Alt, Frederick; Casellas, Rafael (Springer Science and Business Media LLC, 2019-10-30)
      Antibody class switch recombination (CSR) in B lymphocytes replaces immunoglobulin heavy chain locus (Igh) Cμ constant region exons (CHs) with one of six CHs lying 100–200 kb downstream1. Each CH is flanked upstream by an ...
    • Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases 

      Frock, Richard L.; Hu, Jiazhi; Meyers, Robin M.; Ho, Yu-Jui; Kii, Erina; Alt, Frederick W. (2014)
      Although great progress has been made in the characterization of off-target effects of engineered nucleases, sensitive and unbiased genome-wide methods for the detection of off-target cleavage events and potential collateral ...
    • Immature B cells preferentially switch to IgE with increased direct Sμ to Sε recombination 

      Wesemann, Duane Robert; Magee, Jennifer; Boboila, Cristian; Calado, Dinis Pedro; Gallagher, Michael P.; Portuguese, Andrew J.; Manis, John P.; Zhou, Xiaolong; Recher, Mike; Rajewsky, Klaus; Notarangelo, Luigi D.; Alt, Frederick W. (The Rockefeller University Press, 2011)
      Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed Cμ (IgM) constant regions (C(H)) exons with downstream C(H) exons. Stimulation of B cells with anti-CD40 plus interleukin-4 ...
    • Investigating Mechanisms of DNA Double Strand Break Joining of Switch Regions During IgH Class Switch Recombination 

      Panchakshari, Rohit (2016-05-19)
      During B cell development, RAG endonuclease cleaves immunoglobulin heavy chain (IgH) V, D, and J gene segments and orchestrates their fusion as deletional events that assemble a V(D)J exon in the same transcriptional ...
    • Localized DNA Demethylation at Recombination Intermediates during Immunoglobulin Heavy Chain Gene Assembly 

      Selimyan, Roza; Gerstein, Rachel M.; Ivanova, Irina; Precht, Patricia; Subrahmanyam, Ramesh; Perlot, Thomas; Alt, Frederick W.; Sen, Ranjan (Public Library of Science, 2013)
      Multiple epigenetic marks have been proposed to contribute to the regulation of antigen receptor gene assembly via V(D)J recombination. Here we provide a comprehensive view of DNA methylation at the immunoglobulin heavy ...
    • Localized Epigenetic Changes Induced by DH Recombination Restricts Recombinase to DJH Junctions 

      Subrahmanyam, Ramesh; Du, Hansen; Ivanova, Irina; Chakraborty, Tirtha; Ji, Yanhong; Zhang, Yu; Alt, Frederick W.; Schatz, David G.; Sen, Ranjan (2013)
      Immunoglobulin heavy chain (Igh) genes are assembled by sequential rearrangements of diversity (DH) and variable (VH) gene segments. Three critical constraints govern VH recombination. These include timing (VH recombination ...
    • Loop Extrusion Mediates Physiological IgH Locus Contraction For RAG Scanning 

      Dai, Hai-Qiang; Hu, Hongli; Lou, Jiangman; Ye, Adam Yongxin; Zhang, Xuefei; Zhang, Yiwen; Zhao, Lijuan; Yoon, Hye; Ba, Zhaoqing; Chapdelaine-Williams, Aimee M.; Kyritsis, Nia; Chen, Huan; Johnson, Kerstin; Lin, Sherry; Conte, Andrea; Casellas, Rafael; Lee, Cheng-Sheng; Alt, Frederick (Springer Science and Business Media LLC, 2021-01-13)
      RAG endonuclease initiates IgH V(D)J recombination in pro-B cells by binding a JH-recombination signal sequence (RSS) within a recombination center (RC) and then linearly scanning upstream chromatin, presented by ...
    • Microbial colonization influences early B-lineage development in the gut lamina propria 

      Wesemann, Duane R.; Portuguese, Andrew J.; Meyers, Robin M.; Gallagher, Michael P.; Cluff-Jones, Kendra; Magee, Jennifer M.; Panchakshari, Rohit A.; Rodig, Scott J.; Kepler, Thomas B.; Alt, Frederick W. (2013)
      The RAG1/RAG2 endonuclease ("RAG") initiates the V(D)J recombination reaction that assembles Ig heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires1. ...
    • Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching 

      Wang, Jing; Alt, Frederick W.; Gostissa, Monica; Datta, Abhishek; Murphy, Michael C.; Alimzhanov, Marat B.; Coakley, Kristen M.; Rajewsky, Klaus; Manis, John P.; Yan, Catherine T. (The Rockefeller University Press, 2008)
      Nonhomologous end-joining (NHEJ) repairs DNA double-strand breaks (DSBs) during V(D)J recombination in developing lymphocytes and during immunoglobulin (Ig) heavy chain (IgH) class switch recombination (CSR) in peripheral ...
    • Orientation-Specific Joining of AID-initiated DNA Breaks Promotes Antibody Class Switching 

      Dong, Junchao; Panchakshari, Rohit A.; Zhang, Tingting; Zhang, Yu; Hu, Jiazhi; Volpi, Sabrina A.; Meyers, Robin M.; Ho, Yu-Jui; Du, Zhou; Robbiani, Davide F.; Meng, Feilong; Gostissa, Monica; Nussenzweig, Michel C.; Manis, John P.; Alt, Frederick W. (2015)
      During B cell development, RAG endonuclease cleaves immunoglobulin heavy chain (IgH) V, D, and J gene segments and orchestrates their fusion as deletional events that assemble a V(D)J exon in the same transcriptional ...
    • Polζ Ablation in B Cells Impairs the Germinal Center Reaction, Class Switch Recombination, DNA Break Repair, and Genome Stability 

      Schenten, Dominik; Kracker, Sven; Esposito, Gloria; Franco, Sonia; Klein, Ulf; Murphy, Michael C.; Alt, Frederick W.; Rajewsky, Klaus (Rockefeller University Press, 2009)
      Polζ is an error-prone DNA polymerase that is critical for embryonic development and maintenance of genome stability. To analyze its suggested role in somatic hypermutation (SHM) and possible contribution to DNA double-strand ...
    • Role of ATM in Suppressing Oncogenic Translocations and Mature B Cell Lymphomas 

      Tepsuporn, Suprawee (2014-02-25)
      The ATM protein senses DNA double-stranded breaks (DSBs) and facilitates proper repair. B and T lymphocytes of ATM-deficient patients have increased antigen receptor locus translocations associated with aberrant V(D)J ...
    • Sγ3 Switch Sequences Function in Place of Endogenous Sγ1 to Mediate Antibody Class Switching 

      Zarrin, Ali A.; Goff, Peter H.; Senger, Kate; Alt, Frederick W. (The Rockefeller University Press, 2008)
      Immunoglobulin heavy chain (IgH) class switch recombination (CSR) replaces the initially expressed IgH Cμ exons with a set of downstream IgH constant region (CH) exons. Individual sets of CH exons are flanked upstream by ...