Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination Journal Article

Authors: Nicolas, L.; Cols, M.; Choi, J. E.; Chaudhuri, J.; Vuong, B.
Article Title: Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination
Abstract: Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity. © 2018 Nicolas L et al.
Keywords: dna damage; dna repair; gene locus; immunoglobulin; genetic transcription; b lymphocyte; dna strand breakage; somatic hypermutation; activation induced cytidine deaminase; enzyme phosphorylation; immunoglobulin gene; feedback system; molecular interaction; immunoglobulin class switching; enzyme localization; genetic regulation; aid; article; csr
Journal Title: F1000Research
Volume: 7
ISSN: 2046-1402
Publisher: Science Navigation Group  
Date Published: 2018-04-13
Start Page: 458
Language: English
DOI: 10.12688/f1000research.13247.1
PROVIDER: scopus
PMCID: PMC5904731
PUBMED: 29744038
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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