Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination.

ABSTRACT: Class switch recombination generates distinct antibody isotypes critical to a robust adaptive immune system, and defects are associated with autoimmune disorders and lymphomagenesis. Transcription is required during class switch recombination to recruit the cytidine deaminase AID-an essential step for the formation of DNA double-strand breaks-and strongly induces the formation of R loops within the immunoglobulin heavy-chain locus. However, the impact of R loops on double-strand break formation and repair during class switch recombination remains unclear. Here, we report that cells lacking two enzymes involved in R loop removal-senataxin and RNase H2-exhibit increased R loop formation and genome instability at the immunoglobulin heavy-chain locus without impacting its transcriptional activ

SUBMITTER: Zhao H 

PROVIDER: S-EPMC9771370 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature