Activation-induced cytidine deaminase (AID) is the essential and sole B cell-specific factor required for class-switch recombination (CSR) and somatic hypermutation (SHM). However, it is not known how AID differentially regulates these two independent events. Involvement of several cofactors interacting with AID has been indicated by scattered distribution of loss-of-function point mutations and evolutionary conservation of the entire 198-amino-acid protein. Here, we report that human AID mutant proteins with insertions, replacements or truncations in the C-terminal region retained strong SHM activity but almost completely lost CSR activity. These results indicate that AID requires interaction with a cofactor(s) specific to CSR.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/ni964 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ligand-Independent Vitamin D Receptor Actions Essential for Keratinocyte Homeostasis in the Skin.
Int J Mol Sci
January 2025
Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Toyama, Japan.
Recently, we demonstrated that the alopecia observed in vitamin D receptor gene-deficient (-KO) rats is not seen in rats with a mutant VDR(R270L/H301Q), which lacks ligand-binding ability, suggesting that the ligand-independent action of VDR plays a crucial role in maintaining the hair cycle. Since -KO rats also showed abnormalities in the skin, the relationship between alopecia and skin abnormalities was examined. To clarify the mechanism of actions of vitamin D and VDR in the skin, protein composition, and gene expression patterns in the skin were compared among -KO, -R270L/H301Q, and wild-type (WT) rats.
View Article and Find Full Text PDFMethylation of foreign DNA overcomes the restriction barrier of and allows efficient genetic manipulation.
Appl Environ Microbiol
January 2025
Department of Biological Sciences, Minnesota State University Mankato, Mankato, Minnesota, USA.
Unlabelled: causes bacterial cold-water disease (BCWD) in salmonids and other fish, resulting in substantial economic losses in aquaculture worldwide. The mechanisms uses to cause disease are poorly understood. Despite considerable effort, most strains of have resisted attempts at genetic manipulation.
View Article and Find Full Text PDFDeep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations.
Nat Genet
January 2025
Institute of Molecular Oncology, Philipps-University, Marburg, Germany.
The mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells.
View Article and Find Full Text PDFKOnezumi-AID: Automation Software for Efficient Multiplex Gene Knockout Using Target-AID.
Int J Mol Sci
December 2024
Laboratory Animal Resource Center, Transborder Medical Research Center, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
With the groundbreaking advancements in genome editing technologies, particularly CRISPR-Cas9, creating knockout mutants has become highly efficient. However, the CRISPR-Cas9 system introduces DNA double-strand breaks, increasing the risk of chromosomal rearrangements and posing a major obstacle to simultaneous multiple gene knockout. Base-editing systems, such as Target-AID, are safe alternatives for precise base modifications without requiring DNA double-strand breaks, serving as promising solutions for existing challenges.
View Article and Find Full Text PDFPromoter Polymorphism (Allelic Variation) Affects Tacrolimus Treatment Efficacy by Modulating E2F6 Binding Affinity.
Biomedicines
December 2024
Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China.
Background: Tacrolimus is widely used as a first-line immunosuppressant in transplant immunology; however, its clinical application is constrained by the narrow therapeutic index and considerable interindividual variability. In this study, we identified the potential regulatory role of a novel promoter polymorphism, rs4519508 C > T, in the tacrolimus pharmacodynamic pathway.
Methods: Dual-luciferase reporter assays and bioinformatic analysis were applied to assess the impact of allelic variation.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!