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Aid deaminase

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https://www.readbyqxmd.com/read/28933967/aid-biology-a-pathological-and-clinical-perspective
#1
Meenal Choudhary, Anubhav Tamrakar, Amit Kumar Singh, Monika Jain, Ankit Jaiswal, Prashant Kodgire
Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs)...
September 21, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28928744/ccctc-binding-factor-locks-premature-igh-germline-transcription-and-restrains-class-switch-recombination
#2
Ester Marina-Zárate, Arantxa Pérez-García, Almudena R Ramiro
In response to antigenic stimulation B cells undergo class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) to replace the primary IgM/IgD isotypes by IgG, IgE, or IgA. CSR is initiated by activation-induced cytidine deaminase (AID) through the deamination of cytosine residues at the switch (S) regions of IgH. B cell stimulation promotes germline transcription (GLT) of specific S regions, a necessary event prior to CSR because it facilitates AID access to S regions. Here, we show that CCCTC-binding factor (CTCF)-deficient mice are severely impaired in the generation of germinal center B cells and plasma cells after immunization in vivo, most likely due to impaired cell survival...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28875174/improved-base-excision-repair-inhibition-and-bacteriophage-mu-gam-protein-yields-c-g-to-t-a-base-editors-with-higher-efficiency-and-product-purity
#3
Alexis C Komor, Kevin T Zhao, Michael S Packer, Nicole M Gaudelli, Amanda L Waterbury, Luke W Koblan, Y Bill Kim, Ahmed H Badran, David R Liu
We recently developed base editing, the programmable conversion of target C:G base pairs to T:A without inducing double-stranded DNA breaks (DSBs) or requiring homology-directed repair using engineered fusions of Cas9 variants and cytidine deaminases. Over the past year, the third-generation base editor (BE3) and related technologies have been successfully used by many researchers in a wide range of organisms. The product distribution of base editing-the frequency with which the target C:G is converted to mixtures of undesired by-products, along with the desired T:A product-varies in a target site-dependent manner...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28867784/the-complex-interplay-between-dna-injury-and-repair-in-enzymatically-induced-mutagenesis-and-dna-damage-in-b-lymphocytes
#4
REVIEW
Mahnoush Bahjat, Jeroen E J Guikema
Lymphocytes are endowed with unique and specialized enzymatic mutagenic properties that allow them to diversify their antigen receptors, which are crucial sensors for pathogens and mediators of adaptive immunity. During lymphocyte development, the antigen receptors expressed by B and T lymphocytes are assembled in an antigen-independent fashion by ordered variable gene segment recombinations (V(D)J recombination), which is a highly ordered and regulated process that requires the recombination activating gene products 1 & 2 (RAG1, RAG2)...
August 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28827530/development-of-a-comprehensive-set-of-tools-for-genome-engineering-in-a-cold-and-thermo-tolerant-kluyveromyces-marxianus-yeast-strain
#5
Yumiko Nambu-Nishida, Keiji Nishida, Tomohisa Hasunuma, Akihiko Kondo
Kluyveromyces marxianus, a non-conventional thermotolerant yeast, is potentially useful for production of ethanol and other products. This species has a strong tendency to randomly integrate transforming DNA fragments, making necessary the development of more precise methods for gene targeting. In this study, we first demonstrated that K. marxianus NBRC1777 is cold-tolerant, and then established a highly efficient and precise technique for gene editing by introducing genes encoding deaminase-mediated targeted point mutagenesis (Target-AID) and clustered regularly interspaced short palindromic repeats (CRISPR) associated proteins (CRISPR-Cas9)...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790320/activation-induced-cytidine-deaminase-targets-suv4-20-mediated-histone-h4k20-trimethylation-to-class-switch-recombination-sites
#6
Virginia C Rodríguez-Cortez, Paloma Martínez-Redondo, Francesc Català-Moll, Javier Rodríguez-Ubreva, Antonio Garcia-Gomez, Ganesh Poorani-Subramani, Laura Ciudad, Henar Hernando, Arantxa Pérez-García, Carlos Company, José M Urquiza, Almudena R Ramiro, Javier M Di Noia, Alejandro Vaquero, Esteban Ballestar
Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757211/aid-recognizes-structured-dna-for-class-switch-recombination
#7
Qi Qiao, Li Wang, Fei-Long Meng, Joyce K Hwang, Frederick W Alt, Hao Wu
Activation-induced cytidine deaminase (AID) initiates both class switch recombination (CSR) and somatic hypermutation (SHM) in antibody diversification. Mechanisms of AID targeting and catalysis remain elusive despite its critical immunological roles and off-target effects in tumorigenesis. Here, we produced active human AID and revealed its preferred recognition and deamination of structured substrates. G-quadruplex (G4)-containing substrates mimicking the mammalian immunoglobulin switch regions are particularly good AID substrates in vitro...
August 3, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28724724/brct-domain-protein-brit1-influences-class-switch-recombination
#8
Wei-Feng Yen, Ashutosh Chaudhry, Bharat Vaidyanathan, William T Yewdell, Joseph N Pucella, Rahul Sharma, Yulong Liang, Kaiyi Li, Alexander Y Rudensky, Jayanta Chaudhuri
DNA double-strand breaks (DSBs) serve as obligatory intermediates for Ig heavy chain (Igh) class switch recombination (CSR). The mechanisms by which DSBs are resolved to promote long-range DNA end-joining while suppressing genomic instability inherently associated with DSBs are yet to be fully elucidated. Here, we use a targeted short-hairpin RNA screen in a B-cell lymphoma line to identify the BRCT-domain protein BRIT1 as an effector of CSR. We show that conditional genetic deletion of BRIT1 in mice leads to a marked increase in unrepaired Igh breaks and a significant reduction in CSR in ex vivo activated splenic B cells...
July 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716949/biochemical-regulatory-features-of-aid-remain-conserved-from-lamprey-to-humans
#9
Emma M Quinlan, Justin J King, Chris T Amemiya, Ellen Hsu, Mani Larijani
Activation induced cytidine deaminase (AID) is a genome-mutating enzyme that initiates class switch recombination and somatic hypermutation of antibodies in jawed vertebrates. We previously described the biochemical properties of human AID and found that it is an unusual enzyme in that it exhibits binding affinities for its substrate DNA and catalytic rates several orders of magnitude higher and lower, respectively, than a typical enzyme. Recently, we solved the functional structure of AID and demonstrated that these properties are due to non-specific DNA binding on its surface, along with a catalytic pocket that predominantly assumes a closed conformation...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28708393/selective-deamination-of-mutagens-by-a-mycobacterial-enzyme
#10
Vandana Gaded, Ruchi Anand
Structure-based methods are powerful tools that are being exploited to unravel new functions with therapeutic advantage. Here, we report the discovery of a new class of deaminases, predominantly found in mycobacterial species that act on the commercially important s-triazine class of compounds. The enzyme Msd from Mycobacterium smegmatis was taken as a representative candidate from an evolutionarily conserved subgroup that possesses high density of Mycobacterium deaminases. Biochemical investigation reveals that Msd specifically acts on mutagenic nucleobases such as 5-azacytosine and isoguanine and does not accept natural bases as substrates...
July 28, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28707393/malaria-epstein-barr-virus-infection-and-the-pathogenesis-of-burkitt-s-lymphoma
#11
Anthony R Mawson, Suvankar Majumdar
A geographical and causal connection has long been recognized between malaria, Epstein-Barr virus (EBV) infection and Burkitt's lymphoma (BL), but the underlying mechanisms remain obscure. Potential clues are that the malaria parasite Plasmodium falciparum selectively absorbs vitamin A from the host and depends on it for its biological activities; secondly, alterations in vitamin A (retinoid) metabolism have been implicated in many forms of cancer, including BL. The first author has proposed that the merozoite-stage malaria parasite, emerging from the liver, uses its absorbed vitamin A as a cell membrane destabilizer to invade the red blood cells, causing anemia and other signs and symptoms of the disease as manifestations of an endogenous form of hypervitaminosis A (Mawson AR, Path Global Health 2013;107(3):122-9)...
July 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28693209/frequent-aberrant-p53-and-fhit-expression-in-endoscopically-resected-superficial-hypopharyngeal-cancer-and-esophageal-cancer
#12
Sohei Yamamoto, Kazuo Yashima, Soichiro Kawata, Kohei Hosoda, Akihiro Tamoto, Yuichiro Ikebuchi, Kazuya Matsumoto, Koichiro Kawaguchi, Kenichi Harada, Yoshikazu Murawaki, Hajime Isomoto
In the last decade, the incidence rate of detection rate of superficial head, neck and esophageal squamous cell carcinomas has increased with the development of endoscopic imaging techniques. These cancers are thought to arise independently subsequent to tissue exposure to a common carcinogen e.g. alcohol or tobacco. This phenomenon has been termed field cancerization. To determine the molecular background of the development of hypopharyngeal squamous cell carcinomas (HPSCCs) and double esophageal squamous cell carcinomas (DESCCs), the present study immunohistochemically assessed tumor-related protein expression [p53, Fhit (fragile histidine triad), E-cadherin and activation-induced cytidine deaminase (AID)], and subsequently determined the correlation between protein expression and clinicopathological data...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28676801/cd25-b-1a-cells-express-aicda
#13
Hiroaki Kaku, Nichol E Holodick, Joseph R Tumang, Thomas L Rothstein
B-1a cells are innate-like B-lymphocytes producing natural antibodies. Activation-induced cytidine deaminase (AID), a product of the Aicda gene, plays a central role in class-switch recombination and somatic hypermutation in B cells. Although a role for Aicda in B-1a cells has been suggested on the basis of experiments with knock out (KO) mice, whether B-1a cells express Aicda, and if so, which B-1a cell subpopulation expresses Aicda, remains unknown. Here, we demonstrate that B-1 cells express Aicda, but at a level below that expressed by germinal center (GC) B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634398/mutations-in-human-aid-differentially-affect-its-ability-to-deaminate-cytidine-and-5-methylcytidine-in-ssdna-substrates-in-vitro
#14
Lucyna Budzko, Paulina Jackowiak, Karol Kamel, Joanna Sarzynska, Janusz M Bujnicki, Marek Figlerowicz
Activation-induced cytidine deaminase (AID) is known for its established role in antibody production. AID induces the diversification of antibodies by deaminating deoxycytidine (C) within immunoglobulin genes. The capacity of AID to deaminate 5-methyldeoxycytidine (5 mC) and/or 5-hydroxymethyldeoxycytidine (5 hmC), and consequently AID involvement in active DNA demethylation, is not fully resolved. For instance, structural determinants of AID activity on different substrates remain to be identified. To better understand the latter issue, we tested how mutations in human AID (hAID) influence its ability to deaminate C, 5 mC, and 5 hmC in vitro...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630076/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-is-affinity-maturation-a-self-defeating-process-for-eliciting-broad-protection
#15
Christopher T Stamper, Patrick C Wilson
Vaccinations are one of the greatest success stories of modern medicine, saving millions of lives since their widespread adoption. However, several diseases continue to elude highly effective vaccination strategies. Chief among these are human immunodeficiency virus (HIV) and influenza (flu), both of which will require vaccines that can guide the creation of highly mutated, broadly neutralizing antibodies (bnAbs). The generation of bnAbs is hindered by our inability to effectively drive the high levels of affinity maturation required to achieve them in a large number of cells...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28626219/base-excision-repair-proteins-couple-activation-induced-cytidine-deaminase-and-endonuclease-g-during-replication-stress-induced-mll-destabilization
#16
B Gole, E Mian, M Rall, L Wiesmüller
The breakpoint cluster region of the MLL gene (MLLbcr) is frequently rearranged in therapy-related and infant acute leukaemia, but the destabilizing mechanism is poorly understood. We recently proposed that DNA replication stress results in MLLbcr cleavage via Endonuclease G (EndoG) and represents the common denominator of genotoxic therapy-induced MLL destabilization. Here we performed a siRNA screen for new factors involved in replication stress-induced MLL rearrangements employing an EGFP-based reporter system...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28621910/allospecific-memory-b-cell-responses-are-dependent-on-autophagy
#17
M Fribourg, J Ni, F Nina Papavasiliou, Z Yue, P S Heeger, J S Leventhal
Long-lived, donor-reactive memory B cells (Bmems) can produce alloantibodies that mediate transplant injury. Autophagy, an intrinsic mechanism of cell organelle/component recycling, is required for Bmem survival in infectious and model antigen systems, but whether autophagy affects alloreactive Bmem is unknown. We studied mice with an inducible yellow fluorescent protein (YFP) reporter expressed under the activation-induced cytidine deaminase (AID) promoter active in B cells undergoing germinal center reactions...
June 16, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28589361/the-aid-cre-ert2-model-a-tool-for-monitoring-b-cell-immune-responses-and-generating-selective-hybridomas
#18
Simon Le Gallou, Takuya Nojima, Daisuke Kitamura, Jean-Claude Weill, Claude-Agnès Reynaud
Expression of activation-induced cytidine deaminase (AID) is the hallmark of B cells engaged in an immune response in germinal centers. We designed an inducible fate-mapping reporter mouse in which AID-expressing B cells could be timely and irreversibly marked, by knockin at the Aicda locus of a tamoxifen-inducible Cre recombinase. This mouse model allows notably for the long-term follow-up of memory B cells and plasma cells engaged in an immune response. We describe here a protocol to generate hybridomas from small memory subsets that can be easily traced and identified in this mouse line through Cre-activated fluorescent reporters...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28588701/aberrant-expression-of-aid-and-aid-activators-of-nf-%C3%AE%C2%BAb-and-pax5-is-irrelevant-to-ebv-associated-gastric-cancers-but-is-associated-with-carcinogenesis-in-certain-ebv-non-associated-gastric-cancers
#19
Takashi Mohri, Keiko Nagata, Satoshi Kuwamoto, Michiko Matsushita, Hirotsugu Sugihara, Masako Kato, Yasushi Horie, Ichiro Murakami, Kazuhiko Hayashi
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a distinct subtype of gastric cancer characterized by clinicopathological features including lymphoepithelioma-like histology. Aberrant expression of activation-induced cytidine deaminase (AID) as a genomic modulator was demonstrated through pathogen-related nuclear factor κB (NF-κB) signaling in Helicobacter pylori-associated gastric cancer. To elucidate whether or not AID expression is relevant to carcinogenesis in EBVaGC, immunohistochemical expression of AID and AID-regulatory factors between EBVaGC and EBV-non-associated gastric carcinoma (GC) were evaluated, each using 15 cases of GC with lymphoid stroma (GCLS) and other types of GC...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28575114/early-derivation-of-igm-memory-cells-and-bone-marrow-plasmablasts
#20
Amber M Papillion, Kevin J Kenderes, Jennifer L Yates, Gary M Winslow
IgM memory cells are recognized as an important component of B cell memory in mice and humans. Our studies of B cells elicited in response to ehrlichial infection identified a population of CD11c-positive IgM memory cells, and an IgM bone marrow antibody-secreting cell population. The origin of these cells was unknown, although an early T-independent spleen CD11c- and T-bet-positive IgM plasmablast population precedes both, suggesting a linear relationship. A majority of the IgM memory cells detected after day 30 post-infection, also T-bet-positive, had undergone somatic hypermutation, indicating they expressed activation-induced cytidine deaminase (AID)...
2017: PloS One
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