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V(d)J recombination

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https://www.readbyqxmd.com/read/28701730/the-mll-recombinome-of-acute-leukemias-in-2017
#1
C Meyer, T Burmeister, D Gröger, G Tsaur, L Fechina, S Renneville, R Sutton, N C Venn, M Emerenciano, M S Pombo-de-Oliveira, C Barbieri Blunck, B Almeida Lopes, J Zuna, J Trka, P Ballerini, H Lapillonne, M De Braekeleer, G Cazzaniga, L Corral Abascal, V H J van der Velden, E Delabesse, T S Park, S H Oh, M L M Silva, T Lund-Aho, V Juvonen, A S Moore, O Heidenreich, J Vormoor, E Zerkalenkova, Y Olshanskaya, C Bueno, P Menendez, S Teigler-Schlegel, U Zur Stadt, J Lentes, G Göhring, S Kustanovich, O Aleinikova, B W Schäfer, S Kubetzko, H O Madsen, B Gruhn, X Duarte, P Gameiro, E Lippert, S Bidet, J M Cayuela, E Clappier, C N Alonso, C M Zwaan, M M van den Heuvel-Eibrink, S Izraeli, L Trakhtenbrot, P Archer, J Hancock, A Möricke, J Alten, M Schrappe, M Stanulla, S Strehl, A Attarbaschi, M Dworzak, O A Haas, R Panzer-Grümayer, L Sedék, T Szczepański, S Caye, L Suarez, H Cavé, R Marschalek
Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here, we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements habe been identified so far, of which 94 TPGs are now characterized at the molecular level. Thirty-five out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene...
July 13, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28701719/dynamic-gene-expression-response-to-altered-gravity-in-human-t-cells
#2
Cora S Thiel, Swantje Hauschild, Andreas Huge, Svantje Tauber, Beatrice A Lauber, Jennifer Polzer, Katrin Paulsen, Hartwin Lier, Frank Engelmann, Burkhard Schmitz, Andreas Schütte, Liliana E Layer, Oliver Ullrich
We investigated the dynamics of immediate and initial gene expression response to different gravitational environments in human Jurkat T lymphocytic cells and compared expression profiles to identify potential gravity-regulated genes and adaptation processes. We used the Affymetrix GeneChip® Human Transcriptome Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding genes and performed the experiments during a parabolic flight and a suborbital ballistic rocket mission to cross-validate gravity-regulated gene expression through independent research platforms and different sets of control experiments to exclude other factors than alteration of gravity...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696258/effects-of-dna-end-configuration-on-xrcc4-dna-ligase-iv-and-its-stimulation-of-artemis-activity
#3
Christina A Gerodimos, Howard H Y Chang, Go Watanabe, Michael R Lieber
In humans, nonhomologous DNA end-joining (NHEJ) is the major pathway by which DNA double-strand breaks are repaired. Recognition of each broken DNA end by the DNA repair protein Ku is the first step in NHEJ, followed by the iterative binding of nucleases, DNA polymerases, and the XRCC4:DNA ligase IV (X4:LIV) complex in an order influenced by the configuration of the two DNA ends at the break site. The endonuclease Artemis improves joining efficiency by functioning in a complex with DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) that carries out endonucleolytic cleavage of 5' and 3' overhangs...
July 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28659354/structural-and-mechanistic-implications-of-rearrangement-frequencies-within-human-tcrbv-genes
#4
Maryam B Yassai, Wendy Demos, Jack Gorski
The T cell repertoire is a function of thymic V(D)J rearrangement and of peripheral selection. The mature repertoire embodies TCR sequences that are important for survival and can identify important structural aspects of the TCR. Analysis of the circulating TCRBV19 CD8 T cell repertoire showed that a majority of NDN-encoded CDR3 amino acid motifs start at CDR3 position four, well within the V region. Rearrangement at this position indicates that the DNA hairpin loop is not opened at the position adjacent to the recombination signal sequence, but rather is trimmed back three or more bases...
June 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645381/examining-dna-double-strand-break-repair-in-a-cell-cycle-dependent-manner
#5
Janapriya Saha, Shih-Ya Wang, Anthony J Davis
DNA double-strand breaks (DSBs) are deleterious DNA lesions that must be properly repaired to maintain genome stability. Agents, generated both exogenously (environmental radiation, dental X-rays, etc.) and endogenously (reactive oxygen species, DNA replication, V(D)J recombination, etc.), induce numerous DSBs every day. To counter these DSBs, there are two major repair pathways in mammalian cells, nonhomologous end joining (NHEJ) and homologous recombination (HR). NHEJ directly mediates the religation of the broken DNA molecule and is active in all phases of the cell cycle...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28641141/rag2-involves-the-ig%C3%AE%C2%BA-locus-demethylation-during-b-cell-development
#6
Caijun Wu, Yanying Dong, Xiaohui Zhao, Ping Zhang, Mingzhe Zheng, Hua Zhang, Shichang Li, Yaofeng Jin, Yunfeng Ma, Huixun Ren, Yanhong Ji
The genes encoding the immunoglobulin κ light chain are assembled during B cell development by V(D)J recombination. For efficient rearrangement, the Igκ locus must undergo a series of epigenetic changes. One such epigenetic mark is DNA methylation. The mechanism that the Igκ locus is selectively demethylated at the pre-B cell stage has not previously been characterized. Here, we employed bisulfite DNA-modification assays to analyze the methylation status of the Igκ locus in primary pre-B cells from RAG-deficient mice with pre-rearranged Igh knock-in allele...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28636592/quantifiable-predictive-features-define-epitope-specific-t-cell-receptor-repertoires
#7
Pradyot Dash, Andrew J Fiore-Gartland, Tomer Hertz, George C Wang, Shalini Sharma, Aisha Souquette, Jeremy Chase Crawford, E Bridie Clemens, Thi H O Nguyen, Katherine Kedzierska, Nicole L La Gruta, Philip Bradley, Paul G Thomas
T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 10(15) (ref. 1) to as high as 10(61) (ref. 2) possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28630107/pillars-article-a-role-for-histone-acetylation-in-the-developmental-regulation-of-v-d-j-recombination-science-2000-287-495-498
#8
Michelle Taylor McMurry, Michael S Krangel
No abstract text is available yet for this article.
July 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28612717/-paralogy-and-redundancy-maintaining-genome-integrity-during-v-d-j-recombination
#9
Chloé Lescale, Hélène Lenden Hasse, Ludovic Deriano
No abstract text is available yet for this article.
May 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28610800/human-igg-repertoire-of-malaria-antigen-immunized-human-immune-system-his-mice
#10
Raquel Tayar Nogueira, Vincent Sahi, Jing Huang, Moriya Tsuji
Humanized mouse models present an important tool for preclinical evaluation of new vaccines and therapeutics. Here we show the human variable repertoire of antibody sequences cloned from a previously described human immune system (HIS) mouse model that possesses functional human CD4+ T cells and B cells, namely HIS-CD4/B mice. We sequenced variable IgG genes from single memory B-cell and plasma-cell sorted from splenocytes or whole blood lymphocytes of HIS-CD4/B mice that were vaccinated with a human plasmodial antigen, a recombinant Plasmodium falciparum circumsporozoite protein (rPfCSP)...
June 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28606698/comparative-analyses-of-whole-genome-sequences-of-leishmania-infantum-isolates-from-humans-and-dogs-in-northeastern-brazil
#11
D G Teixeira, G R G Monteiro, D R A Martins, M Z Fernandes, V Macedo-Silva, M Ansaldi, P R P Nascimento, M A Kurtz, J A Streit, M F F M Ximenes, R D Pearson, A Miles, J M Blackwell, M E Wilson, A Kitchen, J E Donelson, J P M S Lima, S M B Jeronimo
The genomic sequences of 20 Leishmania infantum isolates collected in northeastern Brazil were compared with each other and with the available genomic sequences of 29 L. infantum/donovani isolates from Nepal and Turkey. The Brazilian isolates were obtained in the early 1990s or since 2009 from patients with visceral or non-ulcerating cutaneous leishmaniasis, asymptomatic humans, or dogs with visceral leishmaniasis. Two isolates were from the blood and bone marrow of the same visceral leishmaniasis patient. All 20 genomic sequences display 99...
June 10, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28591585/tcrd-rearrangement-redirects-a-processive-tcra-recombination-program-to-expand-the-tcra-repertoire
#12
Zachary M Carico, Kingshuk Roy Choudhury, Baojun Zhang, Yuan Zhuang, Michael S Krangel
Adaptive immunity depends on diverse T cell receptor repertoires generated by variable, diversity, and joining (V[D]J) recombination. Here, we define the principles by which combinatorial diversity is generated in the murine Tcra repertoire. Tcra and Tcrd gene segments share the Tcra-Tcrd locus, with interspersed Vα and Vδ segments undergoing Vδ-Dδ-Jδ rearrangement in CD4(-)CD8(-) thymocytes and then multiple rounds of Vα-Jα rearrangement in CD4(+)CD8(+) thymocytes. We document stepwise, highly coordinated proximal-to-distal progressions of Vα and Jα use on individual Tcra alleles, limiting combinatorial diversity...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28588062/secondary-somatic-mutations-restoring-rad51c-and-rad51d-associated-with-acquired-resistance-to-the-parp-inhibitor-rucaparib-in-high-grade-ovarian-carcinoma
#13
Olga Kondrashova, Minh Nguyen, Kristy Shield-Artin, Anna V Tinker, Nelson N H Teng, Maria I Harrell, Michael J Kuiper, Gwo-Yaw Ho, Holly Barker, Maria Jasin, Rohit Prakash, Elizabeth M Kass, Meghan R Sullivan, Gregory J Brunette, Kara A Bernstein, Robert L Coleman, Anne Floquet, Michael Friedlander, Ganessan Kichenadasse, David M O'Malley, Amit M Oza, James X Sun, Liliane Robillard, Lara Maloney, David D L Bowtell, Heidi Giordano, Matthew J Wakefield, Scott H Kaufmann, Andrew D Simmons, Thomas C Harding, Mitch Raponi, Iain A McNeish, Elizabeth M Swisher, Kevin Lin, Clare L Scott
High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC...
June 6, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28571041/cbf1-is-clinically-prognostic-and-serves-as-a-target-to-block-cellular-invasion-and-chemoresistance-of-emt-like-glioblastoma-cells
#14
D Maciaczyk, D Picard, L Zhao, K Koch, D Herrera-Rios, G Li, V Marquardt, D Pauck, T Hoerbelt, W Zhang, D M Ouwens, M Remke, T Jiang, H J Steiger, J Maciaczyk, U D Kahlert
BACKGROUND: Glioblastoma is the most common and most lethal primary brain cancer. CBF1 (also known as Recombination signal Binding Protein for immunoglobulin kappa J, RBPJ) is the cardinal transcriptional regulator of the Notch signalling network and has been shown to promote cancer stem-like cells (CSCs) in glioblastoma. Recent studies suggest that some of the malignant properties of CSCs are mediated through the activation of pro-invasive programme of epithelial-to-mesenchymal transition (EMT)...
June 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28569776/hiv-integrase-inhibitor-elvitegravir-impairs-rag-functions-and-inhibits-v-d-j-recombination
#15
Mayilaadumveettil Nishana, Namrata M Nilavar, Rupa Kumari, Monica Pandey, Sathees C Raghavan
Integrase inhibitors are a class of antiretroviral drugs used for the treatment of AIDS that target HIV integrase, an enzyme responsible for integration of viral cDNA into host genome. RAG1, a critical enzyme involved in V(D)J recombination exhibits structural similarity to HIV integrase. We find that two integrase inhibitors, Raltegravir and Elvitegravir, interfered with the physiological functions of RAGs such as binding, cleavage and hairpin formation at the recombination signal sequence (RSS), though the effect of Raltegravir was limited...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28550350/recent-advances-in-the-study-of-immunodeficiency-and-dna-damage-response
#16
REVIEW
Tomohiro Morio
DNA breaks can be induced by exogenous stimuli or by endogenous stress, but are also generated during recombination of V, D, and J genes (V(D)J recombination), immunoglobulin class switch recombination (CSR). Among various DNA breaks generated, DNA double strand break (DSB) is the most deleterious one. DNA damage response (DDR) is initiated when DSBs are detected, leading to DNA break repair by non-homologous end joining (NHEJ). The process is critically important for the generation of diversity for foreign antigens; and failure to exert DNA repair leads to immunodeficiency such as severe combined immunodeficiency and hyper-IgM syndrome...
May 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28539926/gene-specific-substitution-profiles-describe-the-types-and-frequencies-of-amino-acid-changes-during-antibody-somatic-hypermutation
#17
Zizhang Sheng, Chaim A Schramm, Rui Kong, James C Mullikin, John R Mascola, Peter D Kwong, Lawrence Shapiro
Somatic hypermutation (SHM) plays a critical role in the maturation of antibodies, optimizing recognition initiated by recombination of V(D)J genes. Previous studies have shown that the propensity to mutate is modulated by the context of surrounding nucleotides and that SHM machinery generates biased substitutions. To investigate the intrinsic mutation frequency and substitution bias of SHMs at the amino acid level, we analyzed functional human antibody repertoires and developed mGSSP (method for gene-specific substitution profile), a method to construct amino acid substitution profiles from next-generation sequencing-determined B cell transcripts...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28532656/the-il-33-st2-axis-is-crucial-in-type-2-airway-responses-induced-by-the-staphylococcus-aureus-protease-spld
#18
Andrea R Teufelberger, Maria Nordengrün, Harald Braun, Tania Maes, Katrien De Grove, Gabriele Holtappels, Clara O'Brien, Sharen Provoost, Hamida Hammad, Amanda Gonçalves, Rudi Beyaert, Wim Declercq, Peter Vandenabeele, Dmitri V Krysko, Barbara M Bröker, Claus Bachert, Olga Krysko
BACKGROUND: Chronic airway inflammatory diseases such as chronic rhinosinusitis with nasal polyps and asthma showed increased nasal Staphylococcus aureus (S. aureus) colonization. Serine protease like protein D (SplD) and other closely related proteases secreted by S. aureus have recently been identified as inducers of allergic asthma in humans and mice but their mechanism of action is largely unknown. OBJECTIVE: We investigated the role of recombinant SplD in driving Th2-biased responses and IgE formation in a murine model of allergic asthma...
May 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28532625/v-d-j-recombination-exploits-dna-damage-responses-to-promote-immunity
#19
REVIEW
Rahul Arya, Craig H Bassing
It has been recognized for 40 years that the variable (diversity) joining [V(D)J] recombination-mediated assembly of diverse B and T lymphocyte antigen receptor (AgR) genes is not only essential for adaptive immunity, but also a risk for autoimmunity and lymphoid malignancies. Over the past few years, several studies have revealed that recombination-activating gene (RAG) endonuclease-induced DNA double-strand breaks (DSBs) transcend hazardous intermediates during antigen receptor gene assembly. RAG cleavage within the genomes of lymphocyte progenitors and immature lymphocytes regulates the expression of ubiquitous and lymphocyte-specific gene transcripts to control the differentiation and function of both adaptive and innate immune cell lineages...
July 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28515723/different-somatic-hypermutation-levels-among-antibody-subclasses-disclosed-by-a-new-next-generation-sequencing-based-antibody-repertoire-analysis
#20
Kazutaka Kitaura, Hiroshi Yamashita, Hitomi Ayabe, Tadasu Shini, Takaji Matsutani, Ryuji Suzuki
A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM). Class-switch recombination (CSR) produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS)-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals...
2017: Frontiers in Immunology
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