| Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5. | |
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MedLine Citation:
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PMID: 20887897 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation-induced cytidine deaminase (AID) initiates antibody gene diversification by creating U:G mismatches. However, AID is not specific for antibody genes; Off-target lesions can activate oncogenes or cause chromosome translocations. Despite its importance in these transactions little is known about how AID finds its targets. We performed an shRNA screen to identify factors required for class switch recombination (CSR) of antibody loci. We found that Spt5, a factor associated with stalled RNA polymerase II (Pol II) and single stranded DNA (ssDNA), is required for CSR. Spt5 interacts with AID, it facilitates association between AID and Pol II, and AID recruitment to its Ig and non-Ig targets. ChIP-seq experiments reveal that Spt5 colocalizes with AID and stalled Pol II. Further, Spt5 accumulation at sites of Pol II stalling is predictive of AID-induced mutation. We propose that AID is targeted to sites of Pol II stalling in part via its association with Spt5. |
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Authors:
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Rushad Pavri; Anna Gazumyan; Mila Jankovic; Michela Di Virgilio; Isaac Klein; Camilo Ansarah-Sobrinho; Wolfgang Resch; Arito Yamane; Bernardo Reina San-Martin; Vasco Barreto; Thomas J Nieland; David E Root; Rafael Casellas; Michel C Nussenzweig |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell Volume: 143 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-04 Completed Date: 2010-10-19 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 122-33 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE24178 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals B-Lymphocytes / metabolism* Cell Line Cell Line, Tumor Chromosomal Proteins, Non-Histone / metabolism* Cytidine Deaminase / metabolism* Fibroblasts / metabolism Humans Immunoglobulin Class Switching* Immunoglobulins / genetics Mice RNA Polymerase II / metabolism* Transcriptional Elongation Factors / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI037526/AI/NIAID NIH HHS; R01 AI037526-16/AI/NIAID NIH HHS; R01 AI037526-18/AI/NIAID NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Chromosomal Proteins, Non-Histone; 0/Immunoglobulins; 0/Transcriptional Elongation Factors; 138673-72-0/SPT5 transcriptional elongation factor; EC 2.7.7.-/RNA Polymerase II; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
| Comments/Corrections | |
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