TONSL (tonsoku like, DNA repair protein) functions as a critical component of the MMS22L-TONSL complex that promotes homologous recombination-mediated repair of double-strand breaks at stalled or collapsed replication forks 1. The protein serves as a histone reader that specifically recognizes newly synthesized histones following DNA replication, particularly binding to histone H4 lacking methylation at lysine 20 (H4K20me0) and histone H3.1 1. This histone recognition ability allows TONSL to distinguish post-replicative chr8 states and recruit DNA repair machinery to appropriate sites. Mechanistically, the TONSL-MMS22L complex mediates assembly of RAD51 filaments on single-stranded DNA following histone chaperone-mediated histone replacement and RPA complex eviction from DNA breaks 2. Beyond DNA repair, TONSL demonstrates oncogenic properties, acting as an immortalizing factor in breast epithelial cells and being amplified in approximately 20% of breast cancers 3. TONSL overexpression increases chr8 accessibility to pro-oncogenic transcription factors while limiting tumor suppressor p53 access, and upregulates homologous recombination pathway genes 3. Clinically, TONSL amplification correlates with poor survival in breast cancer patients, making it a potential therapeutic target, with TONSL-amplified cancer cells showing sensitivity to FACT complex inhibitors 3.