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A role for the RNA pol II–associated PAF complex in AID-induced immune diversification

Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspec...

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Autores principales: Willmann, Katharina L., Milosevic, Sara, Pauklin, Siim, Schmitz, Kerstin-Maike, Rangam, Gopinath, Simon, Maria T., Maslen, Sarah, Skehel, Mark, Robert, Isabelle, Heyer, Vincent, Schiavo, Ebe, Reina-San-Martin, Bernardo, Petersen-Mahrt, Svend K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478926/
https://www.ncbi.nlm.nih.gov/pubmed/23008333
http://dx.doi.org/10.1084/jem.20112145
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author Willmann, Katharina L.
Milosevic, Sara
Pauklin, Siim
Schmitz, Kerstin-Maike
Rangam, Gopinath
Simon, Maria T.
Maslen, Sarah
Skehel, Mark
Robert, Isabelle
Heyer, Vincent
Schiavo, Ebe
Reina-San-Martin, Bernardo
Petersen-Mahrt, Svend K.
author_facet Willmann, Katharina L.
Milosevic, Sara
Pauklin, Siim
Schmitz, Kerstin-Maike
Rangam, Gopinath
Simon, Maria T.
Maslen, Sarah
Skehel, Mark
Robert, Isabelle
Heyer, Vincent
Schiavo, Ebe
Reina-San-Martin, Bernardo
Petersen-Mahrt, Svend K.
author_sort Willmann, Katharina L.
collection PubMed
description Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells. The majority of proteins associated with AID belonged to RNA polymerase II elongation and chromatin modification complexes. Besides the two core polymerase subunits, members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID. We show that AID associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain, that depletion of PAF complex members inhibits AID-induced immune diversification, and that the PAF complex can serve as a binding platform for AID on chromatin. A model is emerging of how RNA polymerase II elongation and pausing induce and resolve AID lesions.
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spelling pubmed-34789262013-04-22 A role for the RNA pol II–associated PAF complex in AID-induced immune diversification Willmann, Katharina L. Milosevic, Sara Pauklin, Siim Schmitz, Kerstin-Maike Rangam, Gopinath Simon, Maria T. Maslen, Sarah Skehel, Mark Robert, Isabelle Heyer, Vincent Schiavo, Ebe Reina-San-Martin, Bernardo Petersen-Mahrt, Svend K. J Exp Med Article Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells. The majority of proteins associated with AID belonged to RNA polymerase II elongation and chromatin modification complexes. Besides the two core polymerase subunits, members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID. We show that AID associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain, that depletion of PAF complex members inhibits AID-induced immune diversification, and that the PAF complex can serve as a binding platform for AID on chromatin. A model is emerging of how RNA polymerase II elongation and pausing induce and resolve AID lesions. The Rockefeller University Press 2012-10-22 /pmc/articles/PMC3478926/ /pubmed/23008333 http://dx.doi.org/10.1084/jem.20112145 Text en © 2012 Willmann et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Willmann, Katharina L.
Milosevic, Sara
Pauklin, Siim
Schmitz, Kerstin-Maike
Rangam, Gopinath
Simon, Maria T.
Maslen, Sarah
Skehel, Mark
Robert, Isabelle
Heyer, Vincent
Schiavo, Ebe
Reina-San-Martin, Bernardo
Petersen-Mahrt, Svend K.
A role for the RNA pol II–associated PAF complex in AID-induced immune diversification
title A role for the RNA pol II–associated PAF complex in AID-induced immune diversification
title_full A role for the RNA pol II–associated PAF complex in AID-induced immune diversification
title_fullStr A role for the RNA pol II–associated PAF complex in AID-induced immune diversification
title_full_unstemmed A role for the RNA pol II–associated PAF complex in AID-induced immune diversification
title_short A role for the RNA pol II–associated PAF complex in AID-induced immune diversification
title_sort role for the rna pol ii–associated paf complex in aid-induced immune diversification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478926/
https://www.ncbi.nlm.nih.gov/pubmed/23008333
http://dx.doi.org/10.1084/jem.20112145
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