AIDing chromatin and transcription-coupled orchestration of immunoglobulin class-switch recombination Journal Article

Authors: Vaidyanathan, B.; Yen, W. F.; Pucella, J. N.; Chaudhuri, J.
Article Title: AIDing chromatin and transcription-coupled orchestration of immunoglobulin class-switch recombination
Abstract: Secondary diversification of the antibody repertoire upon antigenic challenge, in the form of immunoglobulin heavy chain (IgH) class-switch recombination (CSR) endows mature, naïve B cells in peripheral lymphoid organs with a limitless ability to mount an optimal humoral immune response, thus expediting pathogen elimination. CSR replaces the default constant (CH) region exons (Cμ) of IgH with any of the downstream CH exons (Cγ, Cε, or Cα), thereby altering effector functions of the antibody molecule. This process depends on, and is orchestrated by, activation-induced deaminase (AID), a DNA cytidine deaminase that acts on single-stranded DNA exposed during transcription of switch (S) region sequences at the IgH locus. DNA lesions thus generated are processed by components of several general DNA repair pathways to drive CSR. Given that AID can instigate DNA lesions and genomic instability, stringent checks are imposed that constrain and restrict its mutagenic potential. In this review, we will discuss how AID expression and substrate specificity and activity is rigorously enforced at the transcriptional, post-transcriptional, post-translational, and epigenetic levels, and how the DNA-damage response is choreographed with precision to permit targeted activity while limiting bystander catastrophe. © 2014 Vaidyanathan, Yen, Pucella and Chaudhuri.
Keywords: protein expression; protein phosphorylation; unclassified drug; review; nonhuman; dna polymerase; dna recombination; dna damage; dna repair; unindexed drug; microrna; smad3 protein; protein stability; protein interaction; class switch recombination; activation induced cytidine deaminase; gene rearrangement; genetic recombination; immune response; transcription factor e2f; myc protein; heat shock protein 90; protein kinase c; immunoglobulin g1; immunoglobulin g3; nuclear localization signal; protein mlh1; histone h2ax; rna polymerase ii; mismatch repair protein pms2; immunoglobulin e; demethylation; nucleophosmin; smad4 protein; helicobacter infection; histone methylation; peptides and proteins; r-loops; immunoglobulin g2b; nucleolin; immunoglobulin class; b lymphocyte activation; microrna 155; transcription factor pax5; transcription factor e2a; stat6 protein; nuclear export signal; human; class-switching; cytidine deamination; ape1 endonuclease; microrna 181b; microrna 361; polypyrimidine tract binding protein 2
Journal Title: Frontiers in Immunology
Volume: 5
ISSN: 1664-3224
Publisher: Frontiers Media S.A.  
Date Published: 2014-03-28
Start Page: Article 120
Language: English
DOI: 10.3389/fimmu.2014.00120
PROVIDER: scopus
PMCID: PMC3975107
PUBMED: 24734031
Notes: Export Date: 1 May 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Wei-Feng Yen
    10 Yen