Nuclease‐independent functions of RAG1 direct distinct DNA damage responses in B cells
| العنوان: | Nuclease‐independent functions of |
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| المؤلفون: | Rachel Johnston, Brendan Mathias, Stephanie J Crowley, Haley A Schmidt, Lynn S White, Nima Mosammaparast, Abby M Green, Jeffrey J Bednarski |
| المصدر: | EMBO reports. 24 |
| بيانات النشر: | EMBO, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Genetics, Molecular Biology, Biochemistry |
| الوصف: | Developing B cells generate DNA double-stranded breaks (DSBs) to assemble immunoglobulin receptor (Ig) genes necessary for the expression of a mature B cell receptor. These physiologic DSBs are made by the RAG endonuclease, which is comprised of the RAG1 and RAG2 proteins. In pre-B cells, RAG-mediated DSBs activate the ATM kinase to coordinate canonical and non-canonical DNA damage responses (DDR) that trigger DSB repair and B cell developmental signals, respectively. Whether this broad cellular response is distinctive to RAG DSBs is poorly understood. To delineate the factors that direct DDR signaling in B cells, we express a tetracycline-inducible Cas9 nuclease in Rag1-deficient pre-B cells. Both RAG- and Cas9-mediated DSBs at Ig genes activate canonical DDR. In contrast, RAG DSBs, but not Cas9 DSBs, induce the non-canonical DDR-dependent developmental program. This unique response to RAG DSBs is, in part, regulated by non-core regions of RAG1. Thus, B cells trigger distinct cellular responses to RAG DSBs through unique properties of the RAG endonuclease that promotes activation of B cell developmental programs. |
| تدمد: | 1469-3178 1469-221X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f9871b890e7d33a85b2eaa53864d9ffTest https://doi.org/10.15252/embr.202255429Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....8f9871b890e7d33a85b2eaa53864d9ff |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14693178 1469221X |
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