File Name: class-switch recombination interplay of transcription dna deamination and dna repair .zip
J Exp Med 11 May ; 5 : — Class switch recombination CSR allows the humoral immune response to exploit different effector pathways through specific secondary antibody isotypes.
- The role of activation-induced deaminase in antibody diversification and genomic instability
- Regulation of AID, the B-cell genome mutator
- Class-switch recombination: interplay of transcription, DNA deamination and DNA repair
The role of activation-induced deaminase in antibody diversification and genomic instability
Since then, tremendous progress has been achieved toward elucidating how AID functions. AID targets the highly repetitive switch regions of the immunoglobulin heavy chain IgH locus to induce DNA double-strand breaks DSBs , which can be rejoined, leading to switch of constant regions of antibody. This review focuses on the mechanisms that provide the specificity of AID targeting to Ig loci and the role of AID in genomic instability. This is a preview of subscription content, access via your institution. Rent this article via DeepDyve.
Regulation of AID, the B-cell genome mutator
The B cell thereby changes from expressing IgM to one producing IgG, IgE, or IgA, with each antibody isotype having a different effector function during an immune reaction. CSR is a multistep reaction requiring transcription through S regions, the DNA cytidine deaminase AID, and the participation of several general DNA repair pathways including base excision repair, mismatch repair, and classical nonhomologous end-joining. In this review, we discuss our current understanding of how transcription through S regions generates substrates for AID-mediated deamination and how AID participates not only in the initiation of CSR but also in the conversion of deaminated residues into DSBs. Additionally, we review the multiple processes that regulate AID expression and facilitate its recruitment specifically to the Ig loci, and how deregulation of AID specificity leads to oncogenic translocations. Finally, we summarize recent data on the potential role of AID in the maintenance of the pluripotent stem cell state during epigenetic reprogramming. The aptitude of the vertebrate immune system to recognize a highly diverse set of antigens is achieved via adaptive immune lymphocytes called B and T cells.
Class-switch recombination: interplay of transcription, DNA deamination and DNA repair
Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins Igs that can recognize and neutralize a seemingly infinite number of antigens. 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.
DNA lesions inflicted by activation-induced deaminase AID instrumentally initiate the processes reshaping immunoglobulin genes in mature B-cells, from local somatic hypermutation SHM to junctions of distant breaks during class switch recombination CSR. Class switching allows B lymphocytes to replace expression of immunoglobin M with that of immunoglobulins G, A or E. The genetic support of class switching, is a unique and large deletion uniquely occuring within the immunoglobulin heavy chain IgH locus. In immunoglobulin light chain loci, AID only stimulates somatic hypermutation. This study identifies the minimal elements necessary for class-switch recombination to occur instead of hypermutation in a locus targeted by AID, i.
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