| Integrated signwaling in developing lymphocytes: The role of DNA damage responses. | |
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MedLine Citation:
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PMID: 23032308 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Lymphocyte development occurs in a stepwise progression through distinct developmental stages. This ordered maturation ensures that cells express a single, non-autoreactive antigen receptor, which is the cornerstone of a diverse adaptive immune response. Expression of a mature antigen receptor requires assembly of the antigen receptor genes by the process of V(D)J recombination, a reaction that joins distant gene segments through DNA double-strand break (DSB) intermediates. These physiologic DSBs are generated by the recombinase-activating gene (RAG) -1 and -2 proteins, and their generation is regulated by lymphocyte and developmental stage-specific signals from cytokine receptors and antigen receptor chains. Collectively, these signals ensure that V(D)J recombination of specific antigen receptor genes occurs at discrete developmental stages. Once generated, RAG-induced DSBs activate the ataxia-telangiectasia mutated (ATM) kinase to orchestrate a multifaceted DNA damage response that ensures proper DSB repair. In response to RAG DSBs, ATM also regulates a cell type-specific transcriptional response, and here we discuss how this genetic program integrates with other cellular cues to regulate lymphocyte development. |
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Authors:
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Jeffrey J Bednarski; Barry P Sleckman |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-03 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 11 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pathology and Immunology; Washington University School of Medicine; St. Louis, MO USA; Department of Pediatrics; Washington University School of Medicine; St. Louis, MO USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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