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Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation
Class switch recombination (CSR) and somatic hypermutation (SHM) are mechanistically related processes initiated by activation-induced cytidine deaminase. Here, we have studied the role of ataxia telangiectasia and Rad3-related protein (ATR) in CSR by analyzing the recombinational junctions, resulti...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118080/ https://www.ncbi.nlm.nih.gov/pubmed/16390936 http://dx.doi.org/10.1084/jem.20050595 |
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author | Pan-Hammarström, Qiang Lähdesmäki, Aleksi Zhao, Yaofeng Du, Likun Zhao, Zhihui Wen, Sicheng Ruiz-Perez, Victor L. Dunn-Walters, Deborah K. Goodship, Judith A. Hammarström, Lennart |
author_facet | Pan-Hammarström, Qiang Lähdesmäki, Aleksi Zhao, Yaofeng Du, Likun Zhao, Zhihui Wen, Sicheng Ruiz-Perez, Victor L. Dunn-Walters, Deborah K. Goodship, Judith A. Hammarström, Lennart |
author_sort | Pan-Hammarström, Qiang |
collection | PubMed |
description | Class switch recombination (CSR) and somatic hypermutation (SHM) are mechanistically related processes initiated by activation-induced cytidine deaminase. Here, we have studied the role of ataxia telangiectasia and Rad3-related protein (ATR) in CSR by analyzing the recombinational junctions, resulting from in vivo switching, in cells from patients with mutations in the ATR gene. The proportion of cells that have switched to immunoglobulin (Ig)A and IgG in the peripheral blood seems to be normal in ATR-deficient (ATRD) patients and the recombined S regions show a normal “blunt end-joining,” but impaired end joining with partially complementary (1–3 bp) DNA ends. There was also an increased usage of microhomology at the μ-α switch junctions, but only up to 9 bp, suggesting that the end-joining pathway requiring longer microhomologies (≥10 bp) may be ATR dependent. The SHM pattern in the Ig variable heavy chain genes is altered, with fewer mutations occurring at A and more mutations at T residues and thus a loss of strand bias in targeting A/T pairs within certain hotspots. These data suggest that the role of ATR is partially overlapping with that of ataxia telangiectasia–mutated protein, but that the former is also endowed with unique functional properties in the repair processes during CSR and SHM. |
format | Text |
id | pubmed-2118080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21180802007-12-13 Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation Pan-Hammarström, Qiang Lähdesmäki, Aleksi Zhao, Yaofeng Du, Likun Zhao, Zhihui Wen, Sicheng Ruiz-Perez, Victor L. Dunn-Walters, Deborah K. Goodship, Judith A. Hammarström, Lennart J Exp Med Articles Class switch recombination (CSR) and somatic hypermutation (SHM) are mechanistically related processes initiated by activation-induced cytidine deaminase. Here, we have studied the role of ataxia telangiectasia and Rad3-related protein (ATR) in CSR by analyzing the recombinational junctions, resulting from in vivo switching, in cells from patients with mutations in the ATR gene. The proportion of cells that have switched to immunoglobulin (Ig)A and IgG in the peripheral blood seems to be normal in ATR-deficient (ATRD) patients and the recombined S regions show a normal “blunt end-joining,” but impaired end joining with partially complementary (1–3 bp) DNA ends. There was also an increased usage of microhomology at the μ-α switch junctions, but only up to 9 bp, suggesting that the end-joining pathway requiring longer microhomologies (≥10 bp) may be ATR dependent. The SHM pattern in the Ig variable heavy chain genes is altered, with fewer mutations occurring at A and more mutations at T residues and thus a loss of strand bias in targeting A/T pairs within certain hotspots. These data suggest that the role of ATR is partially overlapping with that of ataxia telangiectasia–mutated protein, but that the former is also endowed with unique functional properties in the repair processes during CSR and SHM. The Rockefeller University Press 2006-01-23 /pmc/articles/PMC2118080/ /pubmed/16390936 http://dx.doi.org/10.1084/jem.20050595 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Pan-Hammarström, Qiang Lähdesmäki, Aleksi Zhao, Yaofeng Du, Likun Zhao, Zhihui Wen, Sicheng Ruiz-Perez, Victor L. Dunn-Walters, Deborah K. Goodship, Judith A. Hammarström, Lennart Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation |
title | Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation |
title_full | Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation |
title_fullStr | Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation |
title_full_unstemmed | Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation |
title_short | Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation |
title_sort | disparate roles of atr and atm in immunoglobulin class switch recombination and somatic hypermutation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118080/ https://www.ncbi.nlm.nih.gov/pubmed/16390936 http://dx.doi.org/10.1084/jem.20050595 |
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