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Aid translocation dna

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https://www.readbyqxmd.com/read/29136157/depletion-of-recombination-specific-co-factors-by-the-c-terminal-mutant-of-the-activation-induced-cytidine-deaminase-causes-the-dominant-negative-effect-on-class-switch-recombination
#1
Azza Al Ismail, Afzal Husain, Maki Kobayashi, Tasuku Honjo, Nasim A Begum
Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin (Ig) genes. Studies on in vitro mutagenized AID as well as its mutations in human patients with Hyper-IgM (HIGM)-syndrome type II revealed that C-terminal AID mutations were defective in CSR whereas their DNA cleavage and SHM activities remained intact. The C-terminal mutants of AID were speculated to exert the dominant negative effect on wild type WT AID whereas its mechanism remains unknown...
November 10, 2017: International Immunology
https://www.readbyqxmd.com/read/29122947/phosphorylation-promotes-activation-induced-cytidine-deaminase-activity-at-the-myc-oncogene
#2
Yunxiang Mu, Monika A Zelazowska, Kevin M McBride
Activation-induced cytidine deaminase (AID) is a mutator enzyme that targets immunoglobulin (Ig) genes to initiate antibody somatic hypermutation (SHM) and class switch recombination (CSR). Off-target AID association also occurs, which causes oncogenic mutations and chromosome rearrangements. However, AID occupancy does not directly correlate with DNA damage, suggesting that factors beyond AID association contribute to mutation targeting. CSR and SHM are regulated by phosphorylation on AID serine38 (pS38), but the role of pS38 in off-target activity has not been evaluated...
November 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29040604/associations-of-plasma-cytokine-and-microbial-translocation-biomarkers-with-immune-reconstitution-inflammatory-syndrome
#3
Varghese George, Linda Harrison, Margaret Roach, Xiao-Dong Li, Camlin Tierney, Margaret A Fischl, Judith Aberg, Pablo Tebas, David M Asmuth, Richard B Pollard, Catherine Godfrey, Savita Pahwa
A nested case-cohort study was performed in participants of a clinical trial of first-line human immunodeficiency virus treatments to investigate plasma biomarkers of inflammation and microbial translocation for their association with immune reconstitution inflammatory syndrome (IRIS). Fifty-one of 1452 participants with baseline CD4 count <350 cells/μL developed IRIS. Plasma from 51 IRIS cases, including 6 stratified by preenrollment CD4 count ≤200 cells/μL, were analyzed and compared to 94 non-IRIS controls...
October 13, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28936406/gut-microbiome-based-therapeutics-in-liver-cirrhosis-basic-consideration-for-the-next-step
#4
REVIEW
Hiroshi Fukui
Infections account for significant morbidity and mortality in liver cirrhosis and most are related to the gut microbiome. Fecal dysbiosis, characterized by an overgrowth of potentially pathogenic bacteria and a decrease in autochthonous non-pathogenic bacteria, becomes prominent with the progression of liver cirrhosis. In cirrhotic patients, disruption of the intestinal barrier causes intestinal hyperpermeability (i.e. leaky gut), which is closely related to gut dysmotility, dysbiosis and small intestinal bacterial overgrowth and may induce pathological bacterial translocation...
September 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28733577/skin-renewal-activity-of-non-thermal-plasma-through-the-activation-of-%C3%AE-catenin-in-keratinocytes
#5
J H Choi, Y S Song, K Song, H J Lee, J W Hong, G C Kim
For recent years, devices that generate non-thermal plasma (NTP) have been introduced into the field of dermatology. Since NTP has demonstrated strong anti-pathogenic activity with safety of use, NTP was first applied to sterilize the skin surface to aid in the healing of various kinds of skin diseases. However, the effect of NTP on skin regeneration has not yet been fully explored. In this study, the effect of NTP on the growth of keratinocytes was tested using the HaCaT human keratinocyte cell line and HRM2 hairless mice...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607006/nr4a2-promotes-dna-double-strand-break-repair-upon-exposure-to-uvr
#6
Kelvin Yin, Yash Chhabra, Romain Tropée, Yi Chieh Lim, Mitchell Fane, Eloise Dray, Richard A Sturm, Aaron G Smith
Exposure of melanocytes to ultraviolet radiation (UVR) induces the formation of UV lesions that can produce deleterious effects in genomic DNA. Encounters of replication forks with unrepaired UV lesions can lead to several complex phenomena, such as the formation of DNA double-strand breaks (DSBs). The NR4A family of nuclear receptors are transcription factors that have been associated with mediating DNA repair functions downstream of the MC1R signaling pathway in melanocytes. In particular, emerging evidence shows that upon DNA damage, the NR4A2 receptor can translocate to sites of UV lesion by mechanisms requiring post-translational modifications within the N-terminal domain and at a serine residue in the DNA-binding domain at position 337...
June 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28532341/pterostilbene-protects-against-uvb-induced-photo-damage-through-a-phosphatidylinositol-3-kinase-dependent-nrf2-are-pathway-in-human-keratinocytes
#7
Huaping Li, Na Jiang, Bihua Liang, Qing Liu, Erting Zhang, Liqian Peng, Huiyan Deng, Runxiang Li, Zhenjie Li, Huilan Zhu
OBJECTIVE: Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes. METHODS: Human keratinocytes were pretreated with Pter (5 and 10 μM) for 24 h prior to UVB irradiation (300 mJ/cm(2))...
May 22, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28388279/investigation-of-aid-dicer-and-drosha-expressions-in-patients-with-chronic-lymphocytic-leukemia
#8
Metin Yusuf Gelmez, Ender Coskunpinar, Basak Saracoglu, Gunnur Deniz, Melih Aktan
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries. Cytogenetic lesions such as del13q14, del11q22.3, and del17p13 are identified in 50-60% of patients. Activation-induced cytidine deaminase (AID) plays a central role in somatic hyper mutation (SHM) and class switch recombination (CSR) and functions on Ig genes, but also target non-Ig genes, and over-expression of AID can lead to point mutations or translocations in non-Ig genes such as IgH/Myc translocation. Dicer and Drosha, which have a role in activation process of miRNA, also act in a double-strand DNA break (DSB) repair mechanism...
July 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28360415/hiv-tat-induces-a-prolonged-myc-relocalization-next-to-igh-in-circulating-b-cells
#9
D Germini, T Tsfasman, M Klibi, R El-Amine, A Pichugin, O V Iarovaia, C Bilhou-Nabera, F Subra, Y Bou Saada, A Sukhanova, D Boutboul, M Raphaël, J Wiels, S V Razin, S Bury-Moné, E Oksenhendler, M Lipinski, Y S Vassetzky
With combined antiretroviral therapy (cART), the risk for HIV-infected individuals to develop a non-Hodgkin lymphoma is diminished. However, the incidence of Burkitt lymphoma (BL) remains strikingly elevated. Most BL present a t(8;14) chromosomal translocation which must take place at a time of spatial proximity between the translocation partners. The two partner genes, MYC and IGH, were found colocalized only very rarely in the nuclei of normal peripheral blood B-cells examined using 3D-FISH while circulating B-cells from HIV-infected individuals whose exhibited consistently elevated levels of MYC-IGH colocalization...
November 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28188246/cutting-edge-the-transcription-factor-sox2-regulates-aid-expression-in-class-switched-b-cells
#10
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...
March 15, 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
#11
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
#12
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 that 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...
March 30, 2017: Blood
https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#13
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...
July 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
#14
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...
March 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/27998928/the-cell-cycle-restricts-activation-induced-cytidine-deaminase-activity-to-early-g1
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
May 25, 2016: Nature Reviews. Cancer
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