title: Male sterility and enhanced radiation sensitivity in TLS(-/-) mice.
abstract: 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.
authors.affiliation: Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology and the Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kuroda
authors.forename: J
authors.initials: J
authors.lastname: Sok
authors.forename: L
authors.initials: L
authors.lastname: Webb
authors.forename: H
authors.initials: H
authors.lastname: Baechtold
authors.forename: F
authors.initials: F
authors.lastname: Urano
authors.forename: Y
authors.initials: Y
authors.lastname: Yin
authors.forename: P
authors.initials: P
authors.lastname: Chung
authors.forename: D G
authors.initials: DG
authors.lastname: de Rooij
authors.forename: A
authors.initials: A
authors.lastname: Akhmedov
authors.forename: T
authors.initials: T
authors.lastname: Ashley
authors.forename: D
authors.initials: D
authors.lastname: Ron
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D004622:Embryo, Mammalian / Q000528:radiation effects; D005260:Female; D005347:Fibroblasts; D005835:Genitalia / Q000473:pathology / Q000528:radiation effects; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007150:Immunohistochemistry; D007246:Infertility / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D011995:Recombination, Genetic; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D013094:Spermatozoa / Q000473:pathology / Q000528:radiation effects; D013573:Synaptonemal Complex / Q000235:genetics; D035381:TATA-Binding Protein Associated Factors; D013737:Testis / Q000528:radiation effects; D014157:Transcription Factors / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D035381:TATA-Binding Protein Associated Factors; D014157:Transcription Factors; D012313:RNA