TONSL suppresses polymerase theta-dependent tandem duplications through chromatin-guided repair - PubMed
7 hours ago
- #Genome integrity
- #Tandem duplications
- #Chromatin repair
- TONSL (TONSOKU/tnsl-1) is identified as a key suppressor of tandem duplications (TDs) in genomes.
- Loss of TONSL leads to TDs in two size classes: ~25 kb in rapidly dividing cells and ~300 kb in slower-dividing progenitors.
- TD formation depends on polymerase theta-mediated end joining (TMEJ) and involves break-induced replication (BIR) for expansion.
- TONSL deficiency causes similar TD signatures in both C. elegans and Arabidopsis thaliana, indicating evolutionary conservation.
- TONSL protects genome integrity by suppressing TD formation, with potential implications in cancer and genomic instability.