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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 pre‐meiotic 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.