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A source of the single stranded DNA substrate for activation-induced deaminase during somatic hypermutation
During somatic hypermutation (SHM), activation-induced deaminase (AID) mutates deoxycytidine on single-stranded DNA (ssDNA) generated by the transcription machinery, but the detailed mechanism remains unclear. Here we report a higher abundance of RNA polymerase II (Pol II) at the immunoglobulin heav...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154566/ https://www.ncbi.nlm.nih.gov/pubmed/24923561 http://dx.doi.org/10.1038/ncomms5137 |
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author | Wang, Xiaohua Fan, Manxia Kalis, Susan Wei, Lirong Scharff, Matthew D. |
author_facet | Wang, Xiaohua Fan, Manxia Kalis, Susan Wei, Lirong Scharff, Matthew D. |
author_sort | Wang, Xiaohua |
collection | PubMed |
description | During somatic hypermutation (SHM), activation-induced deaminase (AID) mutates deoxycytidine on single-stranded DNA (ssDNA) generated by the transcription machinery, but the detailed mechanism remains unclear. Here we report a higher abundance of RNA polymerase II (Pol II) at the immunoglobulin heavy chain variable (Igh-V) region compared to the constant region and partially transcribed Igh RNAs, suggesting a slower Pol II progression at Igh-V that could result in some early/premature transcription termination after prolonged pausing/stalling of Pol II. Knocking down RNA exosome complexes, which could decrease premature transcription termination, leads to decreased SHM. Knocking down Spt5, which can augment premature transcription termination, leads to increases in both SHM and the abundance of ssDNA substrates. Collectively, our data support the model that, following the reduction of Pol II progression (pausing or stalling) at the Igh-V, additional steps such as premature transcription termination are involved in providing ssDNA substrates for AID during SHM. |
format | Online Article Text |
id | pubmed-4154566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-41545662014-12-13 A source of the single stranded DNA substrate for activation-induced deaminase during somatic hypermutation Wang, Xiaohua Fan, Manxia Kalis, Susan Wei, Lirong Scharff, Matthew D. Nat Commun Article During somatic hypermutation (SHM), activation-induced deaminase (AID) mutates deoxycytidine on single-stranded DNA (ssDNA) generated by the transcription machinery, but the detailed mechanism remains unclear. Here we report a higher abundance of RNA polymerase II (Pol II) at the immunoglobulin heavy chain variable (Igh-V) region compared to the constant region and partially transcribed Igh RNAs, suggesting a slower Pol II progression at Igh-V that could result in some early/premature transcription termination after prolonged pausing/stalling of Pol II. Knocking down RNA exosome complexes, which could decrease premature transcription termination, leads to decreased SHM. Knocking down Spt5, which can augment premature transcription termination, leads to increases in both SHM and the abundance of ssDNA substrates. Collectively, our data support the model that, following the reduction of Pol II progression (pausing or stalling) at the Igh-V, additional steps such as premature transcription termination are involved in providing ssDNA substrates for AID during SHM. 2014-06-13 /pmc/articles/PMC4154566/ /pubmed/24923561 http://dx.doi.org/10.1038/ncomms5137 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Wang, Xiaohua Fan, Manxia Kalis, Susan Wei, Lirong Scharff, Matthew D. A source of the single stranded DNA substrate for activation-induced deaminase during somatic hypermutation |
title | A source of the single stranded DNA substrate for activation-induced deaminase during somatic hypermutation |
title_full | A source of the single stranded DNA substrate for activation-induced deaminase during somatic hypermutation |
title_fullStr | A source of the single stranded DNA substrate for activation-induced deaminase during somatic hypermutation |
title_full_unstemmed | A source of the single stranded DNA substrate for activation-induced deaminase during somatic hypermutation |
title_short | A source of the single stranded DNA substrate for activation-induced deaminase during somatic hypermutation |
title_sort | source of the single stranded dna substrate for activation-induced deaminase during somatic hypermutation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154566/ https://www.ncbi.nlm.nih.gov/pubmed/24923561 http://dx.doi.org/10.1038/ncomms5137 |
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