Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) by introducing base substitutions into antibody genes, a process enabling antibody affinity maturation in immune response. How a mutator is tamed to precisely and safely generate programmed DNA lesions in a physiological process remains unsettled, as its dysregulation drives lymphomagenesis. Recent research has revealed several hidden features of AID-initiated mutagenesis: preferential activity on flexible DNA substrates, restrained activity within chromatin loop domains, unique DNA repair factors to differentially decode AID-caused lesions, and diverse consequences of aberrant deamination. Here, we depict the multifaceted regulation of AID activity with a focus on emerging concepts/factors and discuss their implications for the design of base editors (BEs) that install somatic mutations to correct deleterious genomic variants.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.tibs.2024.03.011 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Performance of Rapid Clonotyping of Chronic Lymphocytic Leukemia Using Flongle Flow-Cell Nanopore Sequencing of IGH Rearrangements.
Eur J Haematol
September 2025
Haematology-Pathology Research Laboratory, Research Unit for Haematology and Research Unit for Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark.
Background: Clonotyping of immunoglobulin heavy chain (IGH) gene rearrangements is critical for diagnosis, prognostication, and measurable residual disease monitoring in chronic lymphocytic leukemia (CLL). Although short-read next-generation sequencing (NGS) platforms, such as Illumina MiSeq, are widely used, they face challenges in spanning full VDJ rearrangements. Long-read sequencing via Oxford Nanopore Technologies (ONT) offers a potential alternative using the compact and cost-effective flow cells.
View Article and Find Full Text PDFIGHA1 and IGHG1 Expression Panel Predicts Anti-PD-L1 Response in Muscle-Invasive Bladder Cancer.
Mol Carcinog
September 2025
Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
B cells located in tertiary lymphoid structures (TLSs) may undergo clonal expansion, somatic hypermutation, isotype switching, and tumor-specific antibody production, suggesting that antibody-producing plasma cells may be involved in antitumor immunity. This study used a combination of single-cell sequencing (five samples from our center, and four samples from PRJNA662018) and spatial transcriptome (one sample from our center, and four samples from GSE169379) research methods to investigate the relationship between TLSs and the immunoglobulin repertoire in muscle invasive bladder cancer (MIBC). 405 patients with MIBC from TCGA and 348 patients with metastatic urothelial carcinoma on PD-L1 inhibitor treatment from the IMvigor210 trial were included in this study.
View Article and Find Full Text PDFIntrapatient genomic divergence across multiple primary tumors in young Korean patients.
Korean J Clin Oncol
August 2025
Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.
Purpose: Multiple primary tumors arising in the same individual pose challenges for precision oncology, particularly in the context of hereditary cancer syndromes such as Lynch syndrome. While these tumors may originate from a shared germline predisposition, it remains unclear whether they also share somatic alterations that could be therapeutically exploited. This study aimed to characterize the extent of somatic genomic overlap between synchronous or metachronous gastric and colorectal cancers within young Korean patients.
View Article and Find Full Text PDFLymphoma driver mutations at the root of somatic evolution of nerve-damaging autoantibodies in myelin associated glycoprotein neuropathy.
J Autoimmun
September 2025
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; Cellular Genomics Futures Institute & School of Biomedical Sciences, UNSW Sydney, Australia. Electronic address:
Background: In autoimmune disease it is not understood how self-reactive B cells escape immune tolerance checkpoints to produce pathogenic autoantibodies.
Objective: In patients with demyelinating polyneuropathy caused by IgM autoantibodies against myelin associated glycoprotein (MAG) and the sulphated trisaccharide CD57, we aimed to test the hypothesis that B cells making the autoantibody escaped tolerance by acquiring lymphoma driver somatic mutations.
Methods: Deep single-cell RNA, DNA, flow cytometric and antibody specificity analysis of blood from three patients with MAG neuropathy.
The B cell dilemma: Diversity or fidelity?
DNA Repair (Amst)
August 2025
Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Laboratory of Genome Diversification & Integrity, Berlin, Germany; Charité-Universitätsmedizin Berlin, Berlin 10117, Germany. Electronic address:
The ability of B lymphocytes to diversify immunoglobulin (Ig) genes is central to the generation of high-affinity, class-switched antibodies and the establishment of effective humoral immunity. This diversification is achieved through three DNA remodeling processes that occur at defined stages of B cell development and maturation: V(D)J recombination, somatic hypermutation (SHM), and class switch recombination (CSR). These reactions all rely on the induction of programmed DNA lesions at Ig genes and their productive resolution by ubiquitous DNA repair pathways.
View Article and Find Full Text PDF