Document Detail


p21 is dispensable for AID-mediated class switch recombination and mutagenesis of immunoglobulin genes during somatic hypermutation.
MedLine Citation:
PMID:  21288574     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In B cells, activation-induced cytidine deaminase (AID) induces somatic hypermutation (SHM) at rearranged immunoglobulin (Ig) variable (V) regions. Previous studies have shown that both monoubiquitination of proliferating cell nuclear antigen (PCNA) and translesional DNA polymerase activity are important for inducing mutagenesis during SHM. Regulation of PCNA ubiquitination by p21, also known as Cdkn1a and p21(Cip1/Waf1), is an important mechanism that controls mutation loads in mammalian cells. In this study, we have assessed whether p21 has an in vivo function in regulating mutagenesis in B cells by analyzing SHM frequency in p21-deficient mice. Our results show that p21 is dispensable for SHM. This suggests that, during SHM of Ig genes, p21 does not act to regulate mutagenesis load. We also show that p21 transcript levels are the same in both wildtype and AID-deficient B cells during B cell activation, and that AID-mediated class switch recombination (CSR) is not affected by p21 deficiency; thereby indicating that p21 regulation in B cells is not altered by AID-induced DNA damage and that p21 has no affect on AID-dependent Ig gene diversification. Our results suggest that regulation of p21 in activated B cells is probably more important for maintaining proper cell cycle progression as opposed to promoting SHM of Ig genes.
Authors:
Maryam Shansab; Erik Selsing
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-01
Journal Detail:
Title:  Molecular immunology     Volume:  48     ISSN:  1872-9142     ISO Abbreviation:  Mol. Immunol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-21     Completed Date:  2011-04-05     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  973-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyclin-Dependent Kinase Inhibitor p21 / deficiency,  genetics,  metabolism*
Cytidine Deaminase / metabolism*
Gene Expression Regulation
Genes, Immunoglobulin / genetics*
Immunoglobulin Class Switching / genetics*
Mice
RNA, Messenger / genetics,  metabolism
Recombination, Genetic*
Somatic Hypermutation, Immunoglobulin / genetics*
Grant Support
ID/Acronym/Agency:
AI24465/AI/NIAID NIH HHS; R01 AI024465/AI/NIAID NIH HHS; R01 AI024465-24/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p21; 0/RNA, Messenger; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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