title: AID targeting: old mysteries and new challenges.
abstract: Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and class-switch recombination. AID deamination is not exclusive to immunoglobulin loci; it can instigate DNA lesions in non-immunoglobulin genes and thus stringent checks are in place to constrain and restrict its activity. Recent findings have provided new insights into the mechanisms that target AID activity to specific genomic regions, revealing an involvement for noncoding RNAs associated with polymerase pausing and with enhancer transcription as well as genomic architecture. We review these findings and integrate them into a model for multilevel regulation of AID expression and targeting in immunoglobulin and non-immunoglobulin loci. Within this framework we discuss gaps in understanding, and outline important areas of further research.
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0377, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Chandra
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0377, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bortnick
authors.affiliation: Department of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0377, USA. Electronic address: cmurre@ucsd.edu.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Murre
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D017578:Immunoglobulin Class Switching; D007136:Immunoglobulins / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D014157:Transcription Factors / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D007136:Immunoglobulins; D014157:Transcription Factors; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AID; CSR; SHM; immunoglobulin loci