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Aid translocation dna

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https://www.readbyqxmd.com/read/28188246/cutting-edge-the-transcription-factor-sox2-regulates-aid-expression-in-class-switched-b-cells
#1
Lauren J DiMenna, Wei-Feng Yen, Laura Nicolas, Rahul Sharma, Zara N Saldanha, Jayanta Chaudhuri
IgH class switch recombination (CSR) occurs through the deliberate introduction of activation-induced cytidine deaminase (AID)-instigated DNA double-strand breaks into the IgH loci. Because double-strand breaks are generally highly toxic, mechanisms that regulate AID expression are of much relevance to CSR and genomic integrity; however, effectors of such regulatory processes are still poorly understood. In this article, we show that the transcription factor sex determining region Y-box 2 (Sox2) is expressed in activated B cells, but almost exclusively in those that have undergone CSR...
February 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28176781/rad52-competes-with-ku70-ku86-for-binding-to-s-region-dsb-ends-to-modulate-antibody-class-switch-dna-recombination
#2
Hong Zan, Connie Tat, Zhifang Qiu, Julia R Taylor, Justin A Guerrero, Tian Shen, Paolo Casali
Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S-S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase θ to CSR...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#3
Hiroyoshi Kunimoto, Anna Sophia McKenney, Cem Meydan, Kaitlyn Shank, Abbas Nazir, Franck Rapaport, Benjamin Durham, Francine E Garrett-Bakelman, Elodie Pronier, Alan H Shih, Ari Melnick, Jayanta Chaudhuri, Ross L Levine
Recent studies have reported activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies and hematopoietic specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated...
January 11, 2017: Blood
https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#4
Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, Amber N Brown, Orna Issler, Marie Doyle, Eileen Harrigan, Ezekiell Mouzon, Vincent Vialou, Li Shen, Meelad M Dawlaty, Rudolf Jaenisch, Eric J Nestler
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here, we examined a possible role for the DNA dioxygenase, ten eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28056337/marked-enteropathy-in-an-accelerated-macaque-model-of-aids
#5
Joshua D Croteau, Elizabeth L Engle, Suzanne E Queen, Erin N Shirk, M Christine Zink
Enteropathy in HIV infection is not eliminated with combination antiretroviral therapy and is possibly linked to microbial translocation. We used a rapidly progressing SIV/pigtailed macaque model of HIV to examine enteropathy and microbial translocation. Histologic evidence of intestinal disease was observed in only half of infected macaques during late-stage infection (LSI). Combination antiretroviral therapy initiated during acute infection prevented intestinal disease. In the ileum and colon, enteropathy was associated with increased caspase-3 staining, decreased CD3(+) T cells, and increased SIV-infected cells...
January 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/27998928/the-cell-cycle-restricts-activation-induced-cytidine-deaminase-activity-to-early-g1
#6
Qiao Wang, Kyong-Rim Kieffer-Kwon, Thiago Y Oliveira, Christian T Mayer, Kaihui Yao, Joy Pai, Zhen Cao, Marei Dose, Rafael Casellas, Mila Jankovic, Michel C Nussenzweig, Davide F Robbiani
Activation-induced cytidine deaminase (AID) converts cytosine into uracil to initiate somatic hypermutation (SHM) and class switch recombination (CSR) of antibody genes. In addition, this enzyme produces DNA lesions at off-target sites that lead to mutations and chromosome translocations. However, AID is mostly cytoplasmic, and how and exactly when it accesses nuclear DNA remains enigmatic. Here, we show that AID is transiently in spatial contact with genomic DNA from the time the nuclear membrane breaks down in prometaphase until early G1, when it is actively exported into the cytoplasm...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#7
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27859411/dna-demethylation-pathways-additional-players-and-regulators
#8
Matthias Bochtler, Agnieszka Kolano, Guo-Liang Xu
DNA demethylation can occur passively by "dilution" of methylation marks by DNA replication, or actively and independently of DNA replication. Direct conversion of 5-methylcytosine (5mC) to cytosine (C), as originally proposed, does not occur. Instead, active DNA methylation involves oxidation of the methylated base by ten-eleven translocations (TETs), or deamination of the methylated or a nearby base by activation induced deaminase (AID). The modified nucleotide, possibly together with surrounding nucleotides, is then replaced by the BER pathway...
January 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27372762/quantification-of-oxidized-5-methylcytosine-bases-and-tet-enzyme-activity
#9
M Y Liu, J E DeNizio, R M Kohli
In eukaryotic DNA, cytosine can be enzymatically modified to yield up to four epigenetic base variants. DNA methyltransferases convert cytosine to 5-methylcytosine (mC), which plays critical roles in gene regulation during development. Ten-eleven translocation (TET) enzymes can sequentially oxidize mC to three products: 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxylcytosine (caC). These oxidized bases have been found in numerous mammalian cell types, where they potentially carry out independent epigenetic functions and aid in DNA demethylation...
2016: Methods in Enzymology
https://www.readbyqxmd.com/read/27283771/aberrant-methylation-of-muc1-and-muc4-promoters-are-potential-prognostic-biomarkers-for-pancreatic-ductal-adenocarcinomas
#10
Seiya Yokoyama, Michiyo Higashi, Sho Kitamoto, Monika Oeldorf, Uwe Knippschild, Marko Kornmann, Kosei Maemura, Hiroshi Kurahara, Edwin Wiest, Tomofumi Hamada, Ikumi Kitazono, Yuko Goto, Takashi Tasaki, Tsubasa Hiraki, Kazuhito Hatanaka, Yuko Mataki, Hiroki Taguchi, Shinichi Hashimoto, Surinder K Batra, Akihide Tanimoto, Suguru Yonezawa, Michael A Hollingsworth
Pancreatic cancer is still a disease of high mortality despite availability of diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic neoplasms. MUC1 and MUC4 are high molecular weight transmembrane mucins. These are overexpressed in many carcinomas, and high expression of these molecules is a risk factor associated with poor prognosis. We evaluated the methylation status of MUC1 and MUC4 promoter regions in pancreatic tissue samples from 169 patients with various pancreatic lesions by the methylation specific electrophoresis (MSE) method...
July 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27220482/mechanisms-of-human-lymphoid-chromosomal-translocations
#11
REVIEW
Michael R Lieber
Analysis of chromosomal translocation sequence locations in human lymphomas has provided valuable clues about the mechanism of the translocations and when they occur. Biochemical analyses on the mechanisms of DNA breakage and rejoining permit formulation of detailed models of the human chromosomal translocation process in lymphoid neoplasms. Most human lymphomas are derived from B cells in which a DNA break at an oncogene is initiated by activation-induced deaminase (AID). The partner locus in many cases is located at one of the antigen receptor loci, and this break is generated by the recombination activating gene (RAG) complex or by AID...
25, 2016: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/27133766/recent-adaptations-of-fluorescence-techniques-for-the-determination-of-mechanistic-parameters-of-helicases-and-translocases
#12
Máté Gyimesi, Gábor M Harami, Zsuzsa S Kocsis, Mihály Kovács
Helicases and translocases are nucleic acid (NA)-based molecular motors that use the free energy liberated during the nucleoside triphosphate (NTP, usually ATP) hydrolysis cycle for unidirectional translocation along their NA (DNA, RNA or heteroduplex) substrates. Determination of the kinetic and thermodynamic parameters of their mechanoenzymatic cycle serves as a basis for the exploration of their physiological behavior and various cellular functions. Here we describe how recent adaptations of fluorescence-based solution kinetic methods can be used to determine practically all important mechanistic parameters of NA-based motor proteins...
October 1, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27095148/on-nanopore-dna-sequencing-by-signal-and-noise-analysis-of-ionic-current
#13
Chenyu Wen, Shuangshuang Zeng, Zhen Zhang, Klas Hjort, Ralph Scheicher, Shi-Li Zhang
DNA sequencing, i.e., the process of determining the succession of nucleotides on a DNA strand, has become a standard aid in biomedical research and is expected to revolutionize medicine. With the capability of handling single DNA molecules, nanopore technology holds high promises to become speedier in sequencing at lower cost than what are achievable with the commercially available optics- or semiconductor-based massively parallelized technologies. Despite tremendous progress made with biological and solid-state nanopores, high error rates and large uncertainties persist with the sequencing results...
May 27, 2016: Nanotechnology
https://www.readbyqxmd.com/read/27015368/the-retinoblastoma-protein-regulates-hypoxia-inducible-genetic-programs-tumor-cell-invasiveness-and-neuroendocrine-differentiation-in-prostate-cancer-cells
#14
Mark P Labrecque, Mandeep K Takhar, Rebecca Nason, Stephanie Santacruz, Kevin J Tam, Shabnam Massah, Anne Haegert, Robert H Bell, Manuel Altamirano-Dimas, Colin C Collins, Frank J S Lee, Gratien G Prefontaine, Michael E Cox, Timothy V Beischlag
Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1...
April 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/26873538/distinct-patterns-of-colocalization-of-the-ccnd1-and-cmyc-genes-with-their-potential-translocation-partner-igh-at-successive-stages-of-b-cell-differentiation
#15
Ilya Sklyar, Olga V Iarovaia, Alexey A Gavrilov, Andrey Pichugin, Diego Germini, Tatiana Tsfasman, Gersende Caron, Thierry Fest, Marc Lipinski, Sergey V Razin, Yegor S Vassetzky
The immunoglobulin heavy chain (IGH) locus is submitted to intra-chromosomal DNA breakages and rearrangements during normal B cell differentiation that create a risk for illegitimate inter-chromosomal translocations leading to a variety of B-cell malignancies. In most Burkitt's and Mantle Cell lymphomas, specific chromosomal translocations juxtapose the IGH locus with a CMYC or Cyclin D1 (CCND1) gene, respectively. 3D-fluorescence in situ hybridization was performed on normal peripheral B lymphocytes induced to mature in vitro from a naive state to the stage where they undergo somatic hypermutation (SHM) and class switch recombination (CSR)...
July 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/26740101/combined-deletion-of-xrcc4-and-trp53-in-mouse-germinal-center-b-cells-leads-to-novel-b-cell-lymphomas-with-clonal-heterogeneity
#16
Zhangguo Chen, Mihret T Elos, Sawanee S Viboolsittiseri, Katherine Gowan, Sonia M Leach, Michael Rice, Maxwell D Eder, Kenneth Jones, Jing H Wang
BACKGROUND: Activated B lymphocytes harbor programmed DNA double-strand breaks (DSBs) initiated by activation-induced deaminase (AID) and repaired by non-homologous end-joining (NHEJ). While it has been proposed that these DSBs during secondary antibody gene diversification are the primary source of chromosomal translocations in germinal center (GC)-derived B cell lymphomas, this point has not been directly addressed due to the lack of proper mouse models. METHODS: In the current study, we establish a unique mouse model by specifically deleting a NHEJ gene, Xrcc4, and a cell cycle checkpoint gene, Trp53, in GC B cells, which results in the spontaneous development of B cell lymphomas that possess features of GC B cells...
January 7, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/26681117/activation-induced-deoxycytidine-deaminase-aid-co-transcriptional-scanning-at-single-molecule-resolution
#17
Gayan Senavirathne, Jeffrey G Bertram, Malgorzata Jaszczur, Kathy R Chaurasiya, Phuong Pham, Chi H Mak, Myron F Goodman, David Rueda
Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble...
December 18, 2015: Nature Communications
https://www.readbyqxmd.com/read/26385350/aid-associated-dna-repair-pathways-regulate-malignant-transformation-in-a-murine-model-of-bcl6-driven-diffuse-large-b-cell-lymphoma
#18
Xiwen Gu, Carmen J Booth, Zongzhi Liu, Matthew P Strout
Somatic hypermutation and class-switch recombination of the immunoglobulin (Ig) genes occur in germinal center (GC) B cells and are initiated through deamination of cytidine to uracil by activation-induced cytidine deaminase (AID). Resulting uracil-guanine mismatches are processed by uracil DNA glycosylase (UNG)-mediated base-excision repair and MSH2-mediated mismatch repair (MMR) to yield mutations and DNA strand lesions. Although off-target AID activity also contributes to oncogenic point mutations and chromosome translocations associated with GC and post-GC B-cell lymphomas, the role of downstream AID-associated DNA repair pathways in the pathogenesis of lymphoma is unknown...
January 7, 2016: Blood
https://www.readbyqxmd.com/read/26355458/cell-cycle-regulates-nuclear-stability-of-aid-and-determines-the-cellular-response-to-aid
#19
Quy Le, Nancy Maizels
AID (Activation Induced Deaminase) deaminates cytosines in DNA to initiate immunoglobulin gene diversification and to reprogram CpG methylation in early development. AID is potentially highly mutagenic, and it causes genomic instability evident as translocations in B cell malignancies. Here we show that AID is cell cycle regulated. By high content screening microscopy, we demonstrate that AID undergoes nuclear degradation more slowly in G1 phase than in S or G2-M phase, and that mutations that affect regulatory phosphorylation or catalytic activity can alter AID stability and abundance...
September 2015: PLoS Genetics
https://www.readbyqxmd.com/read/26308889/orientation-specific-joining-of-aid-initiated-dna-breaks-promotes-antibody-class-switching
#20
Junchao Dong, Rohit A Panchakshari, Tingting Zhang, Yu Zhang, Jiazhi Hu, Sabrina A Volpi, Robin M Meyers, Yu-Jui Ho, Zhou Du, Davide F Robbiani, Feilong Meng, Monica Gostissa, Michel C Nussenzweig, John P Manis, Frederick W Alt
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 orientation as adjacent Cμ constant region exons. In mice, six additional sets of constant region exons (CHs) lie 100-200 kilobases downstream in the same transcriptional orientation as V(D)J and Cμ exons. Long repetitive switch (S) regions precede Cμ and downstream CHs. In mature B cells, class switch recombination (CSR) generates different antibody classes by replacing Cμ with a downstream CH (ref...
September 3, 2015: Nature
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