DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programs

BMC Genomics

Research Article

Beth A Helmink¹  Barry P Sleckman¹  Abigail J Holub¹  Stela S Palii²  Cynthia L Innes²  Jill E Hesse²  Richard S Paules² 

[1] Department of Pathology and Immunology, Washington University School of Medicine, 63110, St. Louis, MO, USA;Environmental Stress and Cancer Group, National Institute of Environmental Health Sciences, 27709, Research Triangle Park, NC, USA;

关键词: miR-155;    B cells;    Ionizing radiation;    DNA damage;    Double strand breaks;    Transcriptome profiles;   

DOI  :  10.1186/1471-2164-14-163

 received in 2012-09-18, accepted in 2013-02-27,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundDouble strand (ds) DNA breaks are a form of DNA damage that can be generated from both genotoxic exposures and physiologic processes, can disrupt cellular functions and can be lethal if not repaired properly. Physiologic dsDNA breaks are generated in a variety of normal cellular functions, including the RAG endonuclease-mediated rearrangement of antigen receptor genes during the normal development of lymphocytes. We previously showed that physiologic breaks initiate lymphocyte development-specific transcriptional programs. Here we compare transcriptional responses to physiological DNA breaks with responses to genotoxic DNA damage induced by ionizing radiation.ResultsWe identified a central lymphocyte-specific transcriptional response common to both physiologic and genotoxic breaks, which includes many lymphocyte developmental processes. Genotoxic damage causes robust alterations to pathways associated with B cell activation and increased proliferation, suggesting that genotoxic damage initiates not only the normal B cell maturation processes but also mimics activated B cell response to antigenic agents. Notably, changes including elevated levels of expression of Kras and mmu-miR-155 and the repression of Socs1 were observed following genotoxic damage, reflecting induction of a cancer-prone phenotype.ConclusionsComparing these transcriptional responses provides a greater understanding of the mechanisms cells use in the differentiation between types of DNA damage and the potential consequences of different sources of damage. These results suggest genotoxic damage may induce a unique cancer-prone phenotype and processes mimicking activated B cell response to antigenic agents, as well as the normal B cell maturation processes.

【 授权许可】

Unknown   
© Innes et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.