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.
Kuroda
M
M
Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology and the Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA.
Sok
J
J
Webb
L
L
Baechtold
H
H
Urano
F
F
Yin
Y
Y
Chung
P
P
de Rooij
D G
DG
Akhmedov
A
A
Ashley
T
T
Ron
D
D
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
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