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DNA Double Strand Breaks Occur Independent of AID in Hypermutating Ig Genes

Somatic hypermutation (SHM) and class switch recombination (CSR) take place in B cells of the germinal center (GC) and are associated with DNA double-strand breaks (DNA-DSBs). Transcription favors the generation of DNA-DSBs in the V-regions and switch regions of Ig genes. Both SHM and CSR are contro...

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Autores principales: Bross, Linda, Jacobs, Heinz
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2485413/
https://www.ncbi.nlm.nih.gov/pubmed/14768938
http://dx.doi.org/10.1080/10446670310001626571
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author Bross, Linda
Jacobs, Heinz
author_facet Bross, Linda
Jacobs, Heinz
author_sort Bross, Linda
collection PubMed
description Somatic hypermutation (SHM) and class switch recombination (CSR) take place in B cells of the germinal center (GC) and are associated with DNA double-strand breaks (DNA-DSBs). Transcription favors the generation of DNA-DSBs in the V-regions and switch regions of Ig genes. Both SHM and CSR are controlled by the Activation Induced Cytidine Deaminase (AID), an enzyme exclusively expressed in B cells of the GC. Because AID is capable of deaminating deoxy-cytidine (dC) to deoxy-uracil (dU), it might directly induce nicks (single strand DNA breaks) and also DNA-DSBs via a U-DNA glycosylase mediated base excision repair pathway ('DNA-substrate model'). Alternatively, AID could function like its closest homologue Apobec-1 as a catalytic subunit of a RNA editing holoenzyme ('RNA-substrate model'). To determine whether AID lies upstream or downstream of the DNA lesions found in hypermutating Ig genes, we have analysed the Vλ locus of AID proficient and AID deficient GC B cells for the presence of DNA-DSBs. Although rearranged Vλ genes are preferred targets of SHM we find that AID-proficient and -deficient Vλ1/2-expressing GC B cells display a similar frequency, distribution and sequence preference of DNA-DSBs in rearranged and germline Vλ genes, favoring the idea that AID acts downstream of the DNA lesions to mediate error prone processing.
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spelling pubmed-24854132008-07-25 DNA Double Strand Breaks Occur Independent of AID in Hypermutating Ig Genes Bross, Linda Jacobs, Heinz Clin Dev Immunol Research Article Somatic hypermutation (SHM) and class switch recombination (CSR) take place in B cells of the germinal center (GC) and are associated with DNA double-strand breaks (DNA-DSBs). Transcription favors the generation of DNA-DSBs in the V-regions and switch regions of Ig genes. Both SHM and CSR are controlled by the Activation Induced Cytidine Deaminase (AID), an enzyme exclusively expressed in B cells of the GC. Because AID is capable of deaminating deoxy-cytidine (dC) to deoxy-uracil (dU), it might directly induce nicks (single strand DNA breaks) and also DNA-DSBs via a U-DNA glycosylase mediated base excision repair pathway ('DNA-substrate model'). Alternatively, AID could function like its closest homologue Apobec-1 as a catalytic subunit of a RNA editing holoenzyme ('RNA-substrate model'). To determine whether AID lies upstream or downstream of the DNA lesions found in hypermutating Ig genes, we have analysed the Vλ locus of AID proficient and AID deficient GC B cells for the presence of DNA-DSBs. Although rearranged Vλ genes are preferred targets of SHM we find that AID-proficient and -deficient Vλ1/2-expressing GC B cells display a similar frequency, distribution and sequence preference of DNA-DSBs in rearranged and germline Vλ genes, favoring the idea that AID acts downstream of the DNA lesions to mediate error prone processing. Hindawi Publishing Corporation 2003 /pmc/articles/PMC2485413/ /pubmed/14768938 http://dx.doi.org/10.1080/10446670310001626571 Text en Copyright © 2003 Hindawi Publishing Corporation. http://creativecommons.org/licenses/by/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bross, Linda
Jacobs, Heinz
DNA Double Strand Breaks Occur Independent of AID in Hypermutating Ig Genes
title DNA Double Strand Breaks Occur Independent of AID in Hypermutating Ig Genes
title_full DNA Double Strand Breaks Occur Independent of AID in Hypermutating Ig Genes
title_fullStr DNA Double Strand Breaks Occur Independent of AID in Hypermutating Ig Genes
title_full_unstemmed DNA Double Strand Breaks Occur Independent of AID in Hypermutating Ig Genes
title_short DNA Double Strand Breaks Occur Independent of AID in Hypermutating Ig Genes
title_sort dna double strand breaks occur independent of aid in hypermutating ig genes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2485413/
https://www.ncbi.nlm.nih.gov/pubmed/14768938
http://dx.doi.org/10.1080/10446670310001626571
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