Shieldin and CST co-orchestrate DNA polymerase-dependent tailed-end joining reactions independently of 53BP1-governed repair pathway choice.

ABSTRACT: Tumor suppressor p53-binding protein 1 (53BP1) regulates DNA end joining in lymphocytes, diversifying immune antigen receptors. This involves nucleosome-bound 53BP1 at DNA double-stranded breaks (DSBs) recruiting Rap1-interacting factor 1 homolog (RIF1) and shieldin, a poorly understood DNA-binding complex. The 53BP1-RIF1-shieldin axis is pathological in BRCA1-mutated cancers, blocking homologous recombination (HR) and driving illegitimate nonhomologous end joining (NHEJ). However, how this axis regulates DNA end joining and HR suppression remains unresolved. We investigated shieldin and its interplay with the Ctc1-Stn1-Ten1 (CST) complex, which was recently implicated downstream of 53BP1. Immunophenotypically, mice lacking shieldin or CST are equivalent, with class-switch recombination co

SUBMITTER: King A 

PROVIDER: S-EPMC11753365 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature