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Keywords Activation induced cytidine de...

Activation induced cytidine deaminase

https://read.qxmd.com/read/37949972/activation-induced-cytidine-deaminase-an-antibody-diversification-enzyme-interacts-with-chromatin-modifier-ubn1-in-b-cells
#21
JOURNAL ARTICLE
Ankit Jaiswal, Rajarshi Roy, Anubhav Tamrakar, Amit Kumar Singh, Parimal Kar, Prashant Kodgire
Activation-induced cytidine deaminase (AID) is the key mediator of antibody diversification in activated B-cells by the process of somatic hypermutation (SHM) and class switch recombination (CSR). Targeting AID to the Ig genes requires transcription (initiation and elongation), enhancers, and its interaction with numerous factors. Furthermore, the HIRA chaperon complex, a regulator of chromatin architecture, is indispensable for SHM. The HIRA chaperon complex consists of UBN1, ASF1a, HIRA, and CABIN1 that deposit H3...
November 10, 2023: Scientific Reports
https://read.qxmd.com/read/37910630/cold-blooded-vertebrates-evolved-organized-germinal-center-like-structures
#22
JOURNAL ARTICLE
Yasuhiro Shibasaki, Sergei Afanasyev, Alvaro Fernández-Montero, Yang Ding, Shota Watanabe, Fumio Takizawa, Jesús Lamas, Francisco Fontenla, José Manuel Leiro, Aleksei Krasnov, Pierre Boudinot, J Oriol Sunyer
Germinal centers (GCs) or analogous secondary lymphoid microstructures (SLMs) are thought to have evolved in endothermic species. However, living representatives of their ectothermic ancestors can mount potent secondary antibody (Ab) responses upon infection or immunization, despite the apparent lack of SLMs in these cold-blooded vertebrates. How and where adaptive immune responses are induced in ectothermic species in the absence of GCs or analogous SLMs remains poorly understood. Here we infected a teleost fish (trout) with the parasite Ichthyophthirius multifiliis (Ich) and identified the formation of large aggregates of highly proliferating IgM+ B cells and CD4+ T cells, contiguous to splenic melanomacrophage centers (MMCs)...
November 1, 2023: Science Immunology
https://read.qxmd.com/read/37876256/-helicobacter-pylori-associated-chronic-atrophic-gastritis-and-progression-of-gastric-carcinogenesis
#23
REVIEW
Na Rae Lim, Woo Chul Chung
Chronic inflammation due to a Helicobacter pylori ( H. pylori ) infection is a representative cause of gastric cancer that can promote gastric carcinogenesis by abnormally activating immune cells and increasing the inflammatory cytokines levels. H. pylori infections directly cause DNA double-strand breaks in gastric epithelial cells and genetic damage by increasing the enzymatic activity of cytidine deaminase. Eventually, gastric cancer is induced through dysplasia. Hypermethylation of tumor suppressor genes is an important cause of gastric cancer because of a H...
October 25, 2023: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://read.qxmd.com/read/37845337/split-complementation-of-base-editors-to-minimize-off-target-edits
#24
JOURNAL ARTICLE
Xiangyu Xiong, Kehui Liu, Zhenxiang Li, Fan-Nv Xia, Xue-Ming Ruan, Xionglei He, Jian-Feng Li
Base editors (BEs) empower the efficient installation of beneficial or corrective point mutations in crop and human genomes. However, conventional BEs can induce unpredictable guide RNA (gRNA)-independent off-target edits in the genome and transcriptome due to spurious activities of BE-enclosing deaminases, and current improvements mostly rely on deaminase-specific mutagenesis or exogenous regulators. Here we developed a split deaminase for safe editing (SAFE) system applicable to BEs containing distinct cytidine or adenosine deaminases, with no need of external regulators...
October 16, 2023: Nature Plants
https://read.qxmd.com/read/37790327/increased-aid-results-in-mutations-at-the-crlf2-locus-implicated-in-latin-american-all-health-disparities
#25
Nicholas Pannunzio, Valeria Rangel, Jason Sterrenberg, Aya Garawi, Vyanka Mezcord, Melissa Folkerts, Sabrina Caulderon, Jinglong Wang, Eli Soyfer, Oliver Eng, Jennifer Valerin, Sora Tanjasiri, Fabiola Quintero-Rivera, Selma Masri, Marcus Seldin, Richard Frock, Angela Fleischman
Activation-induced cytidine deaminase (AID) is a B cell-specific base editor required during class switch recombination and somatic hypermutation for B cell maturation and antibody diversification. However, it has also been implicated as a factor in the etiology of several B cell malignancies. Evaluating the AID-induced mutation load in patients at-risk for certain types of blood cancers is critical in assessing disease severity and treatment options. Here, we have developed a digital PCR (dPCR) assay that allows us to track the mutational landscape resulting from AID modification or DNA double-strand break (DSB) formation and repair at sites known to be prone to DSBs...
September 11, 2023: Research Square
https://read.qxmd.com/read/37742176/a-high-throughput-protocol-for-deamination-of-long-single-stranded-dna-and-oligo-pools-containing-complex-sequences
#26
JOURNAL ARTICLE
Yanyan Wang, Senxin Zhang, Xiaoqi Zheng, Leng-Siew Yeap, Fei-Long Meng
Cytidine deaminases as DNA mutators play important roles in immunity and genome stability. Here, we present a high-throughput protocol for deamination of long single-stranded (ss) DNA or oligo pools containing complex sequences. We describe steps for the preparation of both enzyme (activation-induced deaminase, AID) and ssDNA substrates, the deamination reaction, uracil-friendly amplification, and data analysis. This assay can be used to determine the intrinsic mutation profile of a single antibody gene or a pool of selected regions on genomic DNA...
September 23, 2023: STAR protocols
https://read.qxmd.com/read/37683045/replication-cycle-timing-determines-phage-sensitivity-to-a-cytidine-deaminase-toxin-antitoxin-bacterial-defense-system
#27
JOURNAL ARTICLE
Brian Y Hsueh, Micah J Ferrell, Ram Sanath-Kumar, Amber M Bedore, Christopher M Waters
Toxin-antitoxin (TA) systems are ubiquitous two-gene loci that bacteria use to regulate cellular processes such as phage defense. Here, we demonstrate the mechanism by which a novel type III TA system, avcID, is activated and confers resistance to phage infection. The toxin of the system (AvcD) is a deoxycytidylate deaminase that converts deoxycytidines (dC) to dexoyuridines (dU), while the RNA antitoxin (AvcI) inhibits AvcD activity. We have shown that AvcD deaminated dC nucleotides upon phage infection, but the molecular mechanism that activated AvcD was unknown...
September 8, 2023: PLoS Pathogens
https://read.qxmd.com/read/37600817/the-off-target-effects-of-aid-in-carcinogenesis
#28
REVIEW
Junna Jiao, Zhuangwei Lv, Yurong Wang, Liye Fan, Angang Yang
Activation-induced cytidine deaminase (AID) plays a crucial role in promoting B cell diversification through somatic hypermutation (SHM) and class switch recombination (CSR). While AID is primarily associated with the physiological function of humoral immune response, it has also been linked to the initiation and progression of lymphomas. Abnormalities in AID have been shown to disrupt gene networks and signaling pathways in both B-cell and T-cell lineage lymphoblastic leukemia, although the full extent of its role in carcinogenesis remains unclear...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37510234/the-apobec3b-c-783delg-truncating-mutation-is-not-associated-with-an-increased-risk-of-breast-cancer-in-the-polish-population
#29
JOURNAL ARTICLE
Katarzyna Gliniewicz, Wojciech Kluźniak, Dominika Wokołorczyk, Tomasz Huzarski, Klaudia Stempa, Helena Rudnicka, Anna Jakubowska, Marek Szwiec, Joanna Jarkiewicz-Tretyn, Mariusz Naczk, Tomasz Kluz, Tadeusz Dębniak, Jacek Gronwald, Jan Lubiński, Steven A Narod, Mohammad R Akbari, Cezary Cybulski
The APOBEC3B gene belongs to a cluster of DNA-editing enzymes on chromosome 22 and encodes an activation-induced cytidine deaminase. A large deletion of APOBEC3B was associated with increased breast cancer risk, but the evidence is inconclusive. To investigate whether or not APOBEC3B is a breast cancer susceptibility gene, we sequenced this gene in 617 Polish patients with hereditary breast cancer. We detected a single recurrent truncating mutation (c.783delG, p.Val262Phefs) in four of the 617 (0.65%) hereditary cases by sequencing...
June 24, 2023: Genes
https://read.qxmd.com/read/37496419/igh-3-rr-recombination-uncovers-a-non-germinal-center-imprint-and-c-myc-dependent-igh-rearrangement-in-unmutated-chronic-lymphocytic-leukemia
#30
JOURNAL ARTICLE
Israa Al Jamal, Milene Parquet, Kenza Guiyedi, Said Aoufouchi, Morwenna Le Guillou, David Rizzo, Justine Pollet, Marine Dupont, Melanie Boulin, Nathalie Faumont, Hend Boutouil, Fabrice Jardin, Philippe Ruminy, Chahrazed El Hamel, Justine Lerat, Samar Al Hamaoui, Nehman Makdissy, Jean Feuillard, Nathalie Gachard, Sophie Peron
Chronic lymphocytic leukemia (CLL) is an incurable indolent non-Hodgkin lymphoma characterized by tumor B-cells that weakly express a B-cell receptor (BCR). The mutational status of the variable region (IGHV) within the immunoglobulin heavy-chain (IGH) locus is an important prognosis indicator and raises the question of the CLL cell of origin (COO). Mutated IGHV gene CLLs (mCLLs) are genetically imprinted by activation induced-cytidine deaminase (AID). AID is also required for IGH rearrangements: class switch recombination (CSR) and recombination between switch Mu (Sμ) and the 3' regulatory region (3'RR) (Sμ-3'RRrec)...
July 27, 2023: Haematologica
https://read.qxmd.com/read/37407818/therapy-induced-apobec3a-drives-evolution-of-persistent-cancer-cells
#31
JOURNAL ARTICLE
Hideko Isozaki, Ramin Sakhtemani, Ammal Abbasi, Naveed Nikpour, Marcello Stanzione, Sunwoo Oh, Adam Langenbucher, Susanna Monroe, Wenjia Su, Heidie Frisco Cabanos, Faria M Siddiqui, Nicole Phan, Pégah Jalili, Daria Timonina, Samantha Bilton, Maria Gomez-Caraballo, Hannah L Archibald, Varuna Nangia, Kristin Dionne, Amanda Riley, Matthew Lawlor, Mandeep Kaur Banwait, Rosemary G Cobb, Lee Zou, Nicholas J Dyson, Christopher J Ott, Cyril Benes, Gad Getz, Chang S Chan, Alice T Shaw, Justin F Gainor, Jessica J Lin, Lecia V Sequist, Zofia Piotrowska, Beow Y Yeap, Jeffrey A Engelman, Jake June-Koo Lee, Yosef E Maruvka, Rémi Buisson, Michael S Lawrence, Aaron N Hata
Acquired drug resistance to anticancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified1-4 , the underlying molecular mechanisms shaping tumour evolution during treatment are incompletely understood. Genomic profiling of patient tumours has implicated apolipoprotein B messenger RNA editing catalytic polypeptide-like (APOBEC) cytidine deaminases in tumour evolution; however, their role during therapy and the development of acquired drug resistance is undefined...
July 5, 2023: Nature
https://read.qxmd.com/read/37379264/subclonal-tp53-mutations-are-frequent-and-predict-resistance-to-radioimmunotherapy-in-follicular-lymphoma
#32
RANDOMIZED CONTROLLED TRIAL
W Richard Burack, Hongli Li, Diana Adlowitz, Janice M Spence, Lisa M Rimsza, Mazyar Shadman, Catherine M Spier, Mark S Kaminski, John P Leonard, Michael L Leblanc, Sonali M Smith, Jonathan W Friedberg
Although TP53 is commonly mutated in transformed follicular lymphoma, mutations are reported in <5% of pretreatment follicular lymphoma (FL) specimens. We assayed archival follicular B-cell non-Hodgkin lymphoma specimens from a completed clinical trial, Southwest Oncology Group S0016, a phase 3 randomized intergroup trial of CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) chemotherapy plus R-CHOP (rituximab-CHOP) compared with CHOP chemotherapy plus 131-iodine tositumomab (radioimmunotherapy [RIT]-CHOP)...
September 12, 2023: Blood Advances
https://read.qxmd.com/read/37300805/pathogenicity-of-igg-fc-desialylation-and-its-association-with-th17-cells-in-an-animal-model-of-systemic-lupus-erythematosus
#33
JOURNAL ARTICLE
Yuri Nishida, Mirei Shirakashi, Noritaka Hashii, Ran Nakashima, Yoichi Nakayama, Masao Katsushima, Ryu Watanabe, Hideo Onizawa, Ryosuke Hiwa, Hideaki Tsuji, Koji Kitagori, Shuji Akizuki, Akira Onishi, Kosaku Murakami, Hajime Yoshifuji, Masao Tanaka, Tatsuaki Tsuruyama, Akio Morinobu, Motomu Hashimoto
OBJECTIVES: Decreased sialylation of IgG Fc glycans has been reported in autoimmune diseases, but its role in systemic lupus erythematosus (SLE) is not fully understood. In this study, we examined the pathogenicity of IgG desialylation and its association with Th17 in SLE using an animal model. METHODS: B6SKG mice, which develop lupus-like systemic autoimmunity due to the ZAP70 mutation, were used to investigate the pathogenicity of IgG desialylation. The proportion of sialylated IgG was compared between B6SKG and wild-type mice with or without β-glucan treatment-induced Th17 expansion...
June 10, 2023: Modern Rheumatology
https://read.qxmd.com/read/37300695/activation-induced-cytidine-deaminase-displays-an-alternative-co-factor-for-modulating-pim1-expression-in-diffuse-large-b-cell-lymphoma-cell-lines
#34
JOURNAL ARTICLE
Yang Wang, Yinsha Miao, Wen Zhou, Yu Bi, Yanhong Ji, Yunfeng Ma
Diffuse large B cell lymphoma (DLBCL) is a B cell neoplasm characterized by high PIM1 expression, which is responsible for poor prognosis. Activation-induced cytidine deaminase (AID) is closely linked to PIM1 hypermutation in DLBCL. Here, we found that the DNA methyltransferase 1 (DNMT1) level decreased with AID depletion in the DLBCL cell line SU-DHL-4, and increased significantly when AID was highly expressed. The double ablation of AID and DNMT1 contributed to increased PIM1 expression, which initiated faster DLBCL cell proliferation, whereas ten-eleven translocation family member 2 (TET2) decreased with AID deficiency and increased with AID overexpression in DLBCL cell line OCI-LY7...
March 31, 2023: Cellular and Molecular Biology
https://read.qxmd.com/read/37282621/seven-membered-ring-nucleobases-as-inhibitors-of-human-cytidine-deaminase-and-apobec3a
#35
JOURNAL ARTICLE
Harikrishnan M Kurup, Maksim V Kvach, Stefan Harjes, Geoffrey B Jameson, Elena Harjes, Vyacheslav V Filichev
The APOBEC3 (APOBEC3A-H) enzyme family as a part of the human innate immune system deaminates cytosine to uracil in single-stranded DNA (ssDNA) and thereby prevents the spread of pathogenic genetic information. However, APOBEC3-induced mutagenesis promotes viral and cancer evolution, thus enabling the progression of diseases and development of drug resistance. Therefore, APOBEC3 inhibition offers a possibility to complement existing antiviral and anticancer therapies and prevent the emergence of drug resistance, thus making such therapies effective for longer periods of time...
June 7, 2023: Organic & Biomolecular Chemistry
https://read.qxmd.com/read/37253865/b-cell-specific-knockout-of-aid-protects-against-atherosclerosis
#36
JOURNAL ARTICLE
Talin Ebrahimian, France Dierick, Vincent Ta, Maria Kotsiopriftis, Jonathan O'Connor Miranda, Koren K Mann, Alexandre Orthwein, Stephanie Lehoux
Antigen-naive IgM-producing B cells are atheroprotective, whereas mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), would thus be expected to foster atherosclerosis. Yet, AID also plays a major role in the establishment of B cell tolerance. We sought to define whether AID affects atherosclerotic plaque formation. We generated Ldlr-/- chimeras transplanted with bone marrow from Aicda-/- or wild-type (WT) mice, fed a HFD for 14 weeks...
May 30, 2023: Scientific Reports
https://read.qxmd.com/read/37248842/-activation-induced-cytidine-deaminase-aid-involved-in-the-regulation-of-b-cell-immune-senescence
#37
JOURNAL ARTICLE
Jiaping Xiao, Jun Li, Xinsheng Yao
The humoral immune response of B cells is the key to the protection of specific immunity, and immune aging reshapes its production and function. The decreased B cell immune function is an indicator of immune senescence. The impaired humoral immune function mediated by antibody secreted by B cells leads to a decline in the response of elderly individuals to the vaccine. These people are therefore more susceptible to infection and deterioration, and have a higher incidence of tumors and metabolic diseases. Activation-induced cytidine deaminase (AID) is an enzyme that triggers immunoglobulin class conversion recombination (CSR) and somatic high frequency mutation (SHM)...
May 2023: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://read.qxmd.com/read/37245770/crude-polysaccharide-from-danggui-buxue-decoction-enhanced-the-anti-tumor-effect-of-gemcitabine-by-remodeling-tumor-associated-macrophages
#38
JOURNAL ARTICLE
Xiang Zhan, Xin Xu, Pei Zhang, Xiang Wang, Zhaoliang Hu, Wenrui Zhao, Taijun Hang, Min Song
Tumor-associated macrophages (TAMs) with an M2-phenotype mediate gemcitabine resistance to cancer by influencing the metabolic enzymes of gemcitabine and releasing competitive deoxycytidine (dC). Our previous studies showed that Danggui Buxue Decoction (DBD), a traditional Chinese medicinal recipe, enhances the anti-tumor activity of gemcitabine in vivo and alleviates gemcitabine-induced myelosuppression. However, the material basis and exact mechanism underlying its enhanced effects remain unclear. In this study, a bioactive polysaccharide consisting of arabinose, mannose, ribose, and glucose was isolated from DBD...
May 26, 2023: International Journal of Biological Macromolecules
https://read.qxmd.com/read/37224627/apobec3f-is-a-mutational-driver-of-the-human-monkeypox-virus-identified-in-the-2022-outbreak
#39
JOURNAL ARTICLE
Rodolphe Suspène, Kyle A Raymond, Laetitia Boutin, Sophie Guillier, Frédéric Lemoine, Olivier Ferraris, Jean-Nicolas Tournier, Frédéric Iseni, Etienne Simon-Lorière, Jean-Pierre Vartanian
BACKGROUND: On May 6, 2022, a powerful outbreak of monkeypox virus (MPXV) had been reported outside of Africa, with many continuing new cases being reported around the world. Analysis of mutations among the two different lineages present in the 2021 and 2022 outbreaks revealed the presence of G->A mutations occurring in the 5'GpA context, indicative of APOBEC3 cytidine deaminase activity. METHODS: By using a sensitive PCR (3D-PCR) method allowing differential amplification of AT-rich DNA, we analyzed the level of APOBEC3-induced MPXV editing in infected cells and in patients...
May 24, 2023: Journal of Infectious Diseases
https://read.qxmd.com/read/37193683/relationship-between-bcl2-mutations-and-follicular-lymphoma-outcome-in-the-chemoimmunotherapy-era
#40
JOURNAL ARTICLE
Cristina Correia, Matthew J Maurer, Samantha J McDonough, Paula A Schneider, Paige E Ross, Anne J Novak, Andrew L Feldman, James R Cerhan, Susan L Slager, Thomas E Witzig, Bruce W Eckloff, Hu Li, Grzegorz S Nowakowski, Scott H Kaufmann
How to identify follicular lymphoma (FL) patients with low disease burden but high risk for early progression is unclear. Building on a prior study demonstrating the early transformation of FLs with high variant allele frequency (VAF) BCL2 mutations at activation-induced cytidine deaminase (AICDA) sites, we examined 11 AICDA mutational targets, including BCL2, BCL6, PAX5, PIM1, RHOH, SOCS, and MYC, in 199 newly diagnosed grade 1 and 2 FLs. BCL2 mutations with VAF ≥20% occurred in 52% of cases. Among 97 FL patients who did not initially receive rituximab-containing therapy, nonsynonymous BCL2 mutations at VAF ≥20% were associated with increased transformation risk (HR 3...
May 17, 2023: Blood Cancer Journal
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