Non-conservative homologous recombination in human B lymphocytes is promoted by activation-induced cytidine deaminase and transcription
| العنوان: | Non-conservative homologous recombination in human B lymphocytes is promoted by activation-induced cytidine deaminase and transcription |
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| المؤلفون: | Jürgen Bachl, Kerstin Braunschmidt, Joachim W. Ellwart, Maren Mierau, Berit Jungnickel, Friederike Eckardt-Schupp, Eberhard Fritz, André Kutzera, Guido A. Drexler |
| المصدر: | Nucleic Acids Res. 36, 5591-5601 (2008) Nucleic Acids Research |
| بيانات النشر: | Oxford Univ. Press, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Recombination, Genetic, B-Lymphocytes, Lymphoma, B-Cell, Transcription, Genetic, biology, Somatic hypermutation, Cytidine deaminase, Germinal Center, Molecular biology, Cell Line, medicine.anatomical_structure, Cytidine deamination, Transcription (biology), Cell Line, Tumor, Cytidine Deaminase, Genetics, medicine, Activation-induced (cytidine) deaminase, biology.protein, Humans, Somatic Hypermutation, Immunoglobulin, Homologous recombination, Molecular Biology, Gene, B cell |
| الوصف: | During secondary immunoglobulin (Ig) diversification in vertebrates, the sequence of the variable region of Ig genes may be altered by templated or non-templated mechanisms. In both cases, cytidine deamination by activation-induced cytidine deaminase (AID) in the transcribed Ig loci leads to DNA lesions, which are repaired by conservative homologous recombination (HR) during Ig gene conversion, or by non-templated mutagenesis during somatic hypermutation. The molecular basis for the differential use of these two pathways in different species is unclear. While experimental ablation of HR in avian cells performing Ig gene conversion may promote a switch to somatic hypermutation, the activity of HR processes in intrinsically hypermutating mammalian cells has not been measured to date. Employing a functional HR assay in human germinal centre like B cell lines, we detect elevated HR activity that can be enhanced by transcription and AID. Products of such recombination events mostly arise through non-conservative HR pathways, while the activity of conservative HR is low to absent. Our results identify non-conservative HR as a novel DNA transaction pathway promoted by AID and suggest that somatic hypermutation in germinal centre B cells may be based on a physiological suppression of conservative HR. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d27d261c00d35619cdb6ed74cff7aab7Test https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=2980Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d27d261c00d35619cdb6ed74cff7aab7 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |