DNA damage-induced p53 downregulates expression of RAG1 through a negative feedback loop involving miR-34a and FOXP1.

ABSTRACT: During the maturation of pre-B cells, the recombination activating gene 1 and 2 (RAG1/2) endonuclease complex plays a crucial role in coordinating V(D)J recombination by introducing DNA breaks in immunoglobulin (Ig) loci. Dysregulation of RAG1/2 has been linked to the onset of B cell malignancies, yet the mechanisms controlling RAG1/2 in pre-B cells exposed to excessive DNA damage are not fully understood. In this study, we show that DNA damage-induced activation of p53 initiates a negative-feedback loop which rapidly downregulates RAG1 levels. This feedback loop involves ataxia telangiectasia mutated activation, subsequent stabilization of p53, and modulation of microRNA-34a (miR-34a) levels, which is one of the p53 targets. Notably, this loop incorporates transcription factor forkhead bo

SUBMITTER: Ochodnicka-Mackovicova K 

PROVIDER: S-EPMC11625342 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature