H2AX Prevents DNA Breaks from Progressing to Chromosome Breaks and Translocations
| Autor: | Shan Zha, Suprawee Tepsuporn, Zhenkun Lou, Craig H. Bassing, John P. Manis, Catherine T. Yan, Michael M. Murphy, Frederick W. Alt, Julio C. Morales, Melissa M. Adams, Ali A. Zarrin, Monica Gostissa, Junjie Chen, David B. Lombard, Sonia Franco, Phillip B. Carpenter |
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| Rok vydání: | 2006 |
| Předmět: |
DNA Repair
DNA damage chemical and pharmacologic phenomena Chromosomal translocation Biology In Vitro Techniques Immunoglobulin Class Switch Recombination Translocation Genetic Histones chemistry.chemical_compound Mice Cytidine Deaminase Animals Molecular Biology In Situ Hybridization Fluorescence Mice Knockout B-Lymphocytes Chromosome Breakage Cytidine deaminase Cell Biology Molecular biology Immunoglobulin Class Switching Cell biology MDC1 enzymes and coenzymes (carbohydrates) Immunoglobulin class switching chemistry biological phenomena cell phenomena and immunity Chromosome breakage Tumor Suppressor Protein p53 Immunoglobulin Heavy Chains DNA DNA Damage |
| Zdroj: | Molecular Cell. 21(2):201-214 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2006.01.005 |
| Popis: | Histone H2AX promotes DNA double-strand break (DSB) repair and immunoglobulin heavy chain (IgH) class switch recombination (CSR) in B-lymphocytes. CSR requires activation-induced cytidine deaminase (AID) and involves joining of DSB intermediates by end joining. We find that AID-dependent IgH locus chromosome breaks occur at high frequency in primary H2AX-deficient B cells activated for CSR and that a substantial proportion of these breaks participate in chromosomal translocations. Moreover, activated B cells deficient for ATM, 53BP1, or MDC1, which interact with H2AX during the DSB response, show similarly increased IgH locus breaks and translocations. Thus, our findings implicate a general role for these factors in promoting end joining and thereby preventing DSBs from progressing into chromosomal breaks and translocations. As cellular p53 status does not markedly influence the frequency of such events, our results also have implications for how p53 and the DSB response machinery cooperate to suppress generation of lymphomas with oncogenic translocations. |
| Databáze: | OpenAIRE |
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