AID: how does it aid antibody diversity?

Honjo T; Muramatsu M; Fagarasan S

doi:10.1016/j.immuni.2004.05.011

AID: how does it aid antibody diversity?

Honjo T ¹,

Muramatsu M ,

Fagarasan S

Affiliations

1. Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-Ku, Kyoto 606-8501, Japan.
Authors
Honjo T¹
(1 author)

Immunity, 01 Jun 2004, 20(6):659-668
https://doi.org/10.1016/j.immuni.2004.05.011 PMID: 15189732

Review

Abstract

Activation-induced cytidine deaminase (AID) is an essential enzyme to regulate class switch recombination (CSR), somatic hypermutation (SHM), and gene conversion (GC). AID is known to be required for DNA cleavage of S regions in CSR. However, its molecular mechanism is a focus of extensive debate. RNA editing hypothesis postulates that AID edits yet unknown mRNA to generate specific endonucleases for CSR and SHM. By contrast, DNA deamination hypothesis assumes that AID deaminates cytosine in DNA, followed by DNA cleavage by base excision repair enzymes. We discuss available evidence for the two proposed models. Recent findings, namely requirement of protein synthesis for DNA breakage and dispensability of U removal activity of uracil DNA glycosylase, force us to reconsider DNA deamination hypothesis.

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Articles referenced by this article (81)

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Super-enhancer hypermutation alters oncogene expression in B cell lymphoma.
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AID: how does it aid antibody diversity?

Affiliations

Authors

Abstract

Full text links

References

Immunoglobulin gene conversion: insights from bursal B cells and the DT40 cell line.

Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion.

Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice.

Somatic hypermutation in the absence of DNA-dependent protein kinase catalytic subunit (DNA-PK(cs)) or recombination-activating gene (RAG)1 activity.

DNA-dependent protein kinase activity is not required for immunoglobulin class switching.

Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase.

DNA double-strand breaks: prior to but not sufficient in targeting hypermutation.

Ku80 is required for immunoglobulin isotype switching.

The block in immunoglobulin class switch recombination caused by activation-induced cytidine deaminase deficiency occurs prior to the generation of DNA double strand breaks in switch mu region.

Genomic instability in mice lacking histone H2AX.

Citations & impact

Impact metrics

Citations of article over time

Alternative metrics

Article citations

Ataxia Telangiectasia Mutated and MSH2 Control Blunt DNA End Joining in Ig Class Switch Recombination.

Pan-cancer landscape of AID-related mutations, composite mutations, and their potential role in the ICI response.

XLID syndrome gene Med12 promotes Ig isotype switching through chromatin modification and enhancer RNA regulation.

Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity.

Super-enhancer hypermutation alters oncogene expression in B cell lymphoma.

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AID: how does it aid antibody diversity?

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