Male sterility and enhanced radiation sensitivity in TLS-/- mice

TLS (also known as FUS) is an RNA-binding protein that contributes the N-te rminal half of fusion oncoproteins implicated in the development of human l iposarcomas and leukemias, Here we report that male mice homozygous for an induced mutation in TLS are sterile with a marked increase in the number of unpaired and mispaired chromosomal axes in premeiotic spermatocytes. Nucle ar extracts from TLS-/- testes lack an activity capable of promoting pairin g between homologous DNA sequences in vitro, and TLS-/- mice and embryonic fibroblasts exhibit increased sensitivity to ionizing irradiation. These re sults are consistent with a role for TLS in homologous DNA pairing and reco mbination.