Binding of AID to DNA does not correlate with mutator activity Journal Article

Authors: Matthews, A. J.; Husain, S.; Chaudhuri, J.
Article Title: Binding of AID to DNA does not correlate with mutator activity
Abstract: The DNA deaminase activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) by deaminating cytidines to uridines at V region (V) genes and switch (S) regions. The mechanism by which AID is recruited to V genes and S region DNA is poorly understood. In this study, we used the CH12 B lymphoma line to demonstrate that, although S regions can efficiently recruit AID and undergo mutations and deletions, AID neither binds to nor mutates the V gene, thus clearly demonstrating intraimmunoglobulin locus specificity. Depletion of the RNA-binding protein polypyrimidine tract binding protein-2, previously shown to promote recruitment of AID to S regions, enables stable association of AID with the V gene. Surprisingly, AID binding to the V gene does not induce SHM. These results unmask a striking lack of correlation between AID binding and its mutator activity, providing evidence for the presence of factors required downstream of AID binding to effect SHM. Furthermore, our findings suggest that S regions are preferred targets for AID and, aided by polypyrimidine tract binding protein-2, act as "sinks" to sequester AID activity from other genomic regions. Copyright © 2014 by The American Association of Immunologists, Inc.
Keywords: controlled study; unclassified drug; gene mutation; promoter region; gene deletion; nonhuman; animal cell; mouse; gene; protein depletion; protein dna binding; protein targeting; gene locus; immunoglobulin; rna binding protein; b cell lymphoma; somatic hypermutation; activation induced cytidine deaminase; dna; antibody specificity; gene switching; downstream processing; gene activity; priority journal; article; polypyrimidine tract binding protein 2; v gene
Journal Title: Journal of Immunology
Volume: 193
Issue: 1
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2014-07-01
Start Page: 252
End Page: 257
Language: English
DOI: 10.4049/jimmunol.1400433
PROVIDER: scopus
PMCID: PMC4078406
PUBMED: 24879790
Notes: Export Date: 1 August 2014 -- CODEN: JOIMA -- Source: Scopus
Altmetric Score
MSK Authors
  1. Solomon Husain
    2 Husain