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

TLS (also known as FUS) is an RNA-binding protein that contributes the N-terminal half of fusion oncoproteins implicated in the development of human liposarcomas 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. Nuclear extracts from TLS-/- testes lack an activity capable of promoting pairing between homologous DNA sequences in vitro, and TLS-/- mice and embryonic fibroblasts exhibit increased sensitivity to ionizing irradiation. These results are consistent with a role for TLS in homologous DNA pairing and recombination.