Nuclease-independent functions of RAG1 direct distinct DNA damage responses in B cells

ABSTRACT: Developing B cells generate DNA double-stranded breaks (DSBs) to assemble immunoglobulin receptor (Ig) genes necessary for 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 C

SUBMITTER: Ms. Rachel Johnston 

PROVIDER: S-SCDT-10_15252-EMBR_202255429 | biostudies-other |

REPOSITORIES: biostudies-other