Article
Genetics & Heredity
Di Liu, Myron F. Goodman, Phuong Pham, Kefei Yu, Chih-Lin Hsieh, Michael R. Lieber
Summary: Activation-induced deaminase (AID) deaminates cytosine within single-stranded DNA. This study found that AID deamination on duplex DNA substrates is reduced when RNase A is added during transcription. The researchers also discovered that AID acts with similar efficiency on RNA-DNA fusion substrates and DNA-only substrates. Based on these findings, they proposed a model in which the mRNA tail plays a critical role in AID loading and collision with DNA strands.
Article
Multidisciplinary Sciences
Liat Stoler-Barak, Ethan Harris, Ayelet Peres, Hadas Hezroni, Mirela Kuka, Pietro Di Lucia, Amalie Grenov, Neta Gurwicz, Meital Kupervaser, Bon Ham Yip, Matteo Iannacone, Gur Yaari, John D. Crispino, Ziv Shulman
Summary: The protein kinase DYRK1A is essential for B cell-mediated protection from viral infection and effective vaccination by regulating class switch recombination (CSR). It plays a crucial role in B cell immune responses, including attenuating B cell proliferation and promoting the production of pathogen-eliminating antibodies.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yuewen Luo, Xiantao Zhang, Ran Chen, Rong Li, Yang Liu, Junsong Zhang, Qin Liu, Meijun Si, Jun Liu, Bolin Wu, Xuemei Wang, Shijian Wu, Yiwen Zhang, Xu Zhang, Deyin Guo, Xin He, Ting Pan, Hui Zhang
Summary: This study found that the deubiquitinase USP10 can translocate into the nucleus and stabilize nuclear AID protein levels through AKT-mediated phosphorylation. Furthermore, the signals from BCR and TLR synergistically promote the phosphorylation of USP10. Deficiency of USP10 in B cells leads to decreased AID protein levels and reduced production of neutralizing antibodies.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Immunology
Marina Alexeeva, Marivi Nabong Moen, Xiang Ming Xu, Anette Rasmussen, Ingar Leiros, Finn Kirpekar, Arne Klungland, Lene Alsoe, Hilde Nilsen, Svein Bjelland
Summary: Uracil arises in DNA through deamination and replication errors, and its repair by uracil-DNA glycosylase and the base excision repair pathway are crucial in maintaining genomic stability. The mechanisms of DNA incision following uracil excision are still uncertain, but it has been shown that hUNG may play a role in this process and contribute to class switch recombination activity in cells deficient in other repair enzymes.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Kefei Yu
Summary: This mini review discusses recent advances in understanding the function and regulation of AID in B cells, including its molecular structure, advances in high throughput techniques, and the mechanism of AID-mediated class switch recombination. These studies have provided insights into the biochemical properties and function of AID.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Julian Weischedel, Laurence Higgins, Sally Rogers, Anna Gramalla-Schmitz, Paulina Wyrzykowska, Simone Borgoni, Thomas Maccarthy, Richard Chahwan
Summary: Prokaryotic and eukaryotic adaptive immunity have significant differences, but their gene editing mechanisms via Cas9 and activation-induced deaminase (AID) can complement each other. AID-based editor described in this study is able to recapitulate the full spectrum of genomic and epigenomic editing activity, providing insights into AID biology and improving targeted genomic and epigenomic editing.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Ahmed M. Refaat, Mikiyo Nakata, Afzal Husain, Hidetaka Kosako, Tasuku Honjo, Nasim A. Begum
Summary: B cells generate different classes of antibodies through class-switch recombination (CSR) mediated by classical non-homologous end joining (C-NHEJ). The RNA-binding protein HNRNPU promotes the joining of DNA breaks at the switch (S) regions through the 53BP1-shieldin DNA-repair complex. HNRNPU interacts with S region RNA/DNA G-quadruplexes and regulates R-loop and single-stranded DNA (ssDNA) accumulation. It facilitates CSR by forming and stabilizing the C-NHEJ ribonucleoprotein complex and preventing excessive R-loop accumulation, which can lead to genomic instability.
Article
Immunology
Emily Sible, Mary Attaway, Giuseppe Fiorica, Genesis Michel, Jayanta Chaudhuri, Bao Q. Vuong
Summary: This study reveals the critical role of ATM and MSH2 in regulating class-switch recombination (CSR) of immunoglobulins (Ig). ATM promotes this process through its interaction with APE1 via pS38-AID, and ATM and MSH2 cooperate to regulate nonhomologous end joining during CSR.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Yijang Xu, Hang Zhou, Ginell Post, Hong Zan, Paolo Casali
Summary: The study demonstrates that Rad52 mediates IgD CSR through a microhomology-based DNA repair pathway, leading to the expression of IgD in B cells.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Simin Zheng, Allysia J. Matthews, Numa Rahman, Kayleigh Herrick-Reynolds, Emily Sible, Jee Eun Choi, Alec Wishnie, Yan Kee Ng, Daniela Rhodes, Stephen J. Elledge, Bao Q. Vuong
Summary: Class switch recombination (CSR) is the process of B cells switching production from IgM/IgD to other immunoglobulin isotypes. SANBR, identified as a negative regulator of CSR, inhibits CSR through its BTB domain.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Di Liu, Yong-Hwee Eddie Loh, Chih-Lin Hsieh, Michael R. Lieber
Summary: The study reveals that DNA double-strand breaks at translocation breakpoints in human B cell malignancies most frequently occur at CpG sites within 20-600 bp fragile zones and depend on activation-induced deaminase (AID). The ssDNA state in the E2A fragile zone is demonstrated to not require but is increased upon transcription. High C-string density, nascent RNA tails, and direct DNA sequence repeats prolong the ssDNA state and increase AID deamination in the E2A fragile zone.
Article
Immunology
Catherine Tang, Thomas MacCarthy
Summary: Activation-induced deaminase (AID) is an essential enzyme for antibody diversification through somatic hypermutation and class-switch recombination. G-quadruplex (G4) structures have been shown to form in the Ig switch regions, impacting the binding of AID. Computational predictions and biochemical validation reveal high G4 potential in specific human Ig heavy chain V (IGHV) genes, with potential mutability of certain hotspots and coldspots in the V region. These findings suggest functional G4s forming in the Ig V region.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Artem Krantsevich, Catherine Tang, Thomas MacCarthy
Summary: Somatic hypermutation (SHM) of Immunoglobulin (Ig) genes is crucial for antibody affinity maturation in B cells, with the mutagenic enzyme activation induced deaminase (AID) and DNA polymerase eta (Pol eta) playing key roles in introducing mutations at specific hotspots. By studying correlations between mutation sites, it was found that short-range interactions are dominated by AID and/or Pol eta overlapping hotspots, particularly in highly mutating IGHV sub-regions like CDRs. The results suggest that the hotspot preferences for AID and Pol eta have evolved to allow for greater interactions between induced mutations, shedding light on the mechanisms behind antibody affinity maturation.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Audrey Dauba, Ahmed Amine Khamlichi
Summary: CSR is a crucial mechanism in adaptive immune responses, triggered by both T-cell-dependent and T-cell-independent antigens. Transcription of switch sequences and regulation within dynamic chromatin domains play key roles in controlling CSR.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Zhangguo Chen, Jing H. Wang
Summary: Mature B cells express a variety of receptors such as BCR, TLR, CD40, and BAFFR, which transduce signals to regulate physiological and pathological processes including development, survival, proliferation, immune responses, autoimmune diseases, and lymphomagenesis. Class switch recombination allows B cells to switch from expressing IgM to different classes of antibodies with distinct effector functions. Signaling crosstalk between these receptors plays a crucial role in regulating CSR, immune responses, and B cell anergy.
FRONTIERS IN IMMUNOLOGY
(2021)