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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Chromosome Aberrations
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Chromosome Disorders
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Embryo, Mammalian / radiation effects
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Female
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Fibroblasts
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Genitalia / pathology
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Genitalia / radiation effects
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Heterogeneous-Nuclear Ribonucleoproteins
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Immunohistochemistry
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Infertility / genetics*
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Male
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Mice
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Mice, Knockout
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RNA / metabolism
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RNA, Messenger / drug effects
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RNA-Binding Protein FUS
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RNA-Binding Proteins / genetics
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Radiation Tolerance / genetics*
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Radiation, Ionizing
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Recombination, Genetic
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Ribonucleoproteins / genetics*
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Ribonucleoproteins / metabolism
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Spermatozoa / pathology
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Spermatozoa / radiation effects
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Synaptonemal Complex / genetics
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TATA-Binding Protein Associated Factors*
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Testis / radiation effects
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Transcription Factors / metabolism
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Ultraviolet Rays
Substances
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Heterogeneous-Nuclear Ribonucleoproteins
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RNA, Messenger
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RNA-Binding Protein FUS
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RNA-Binding Proteins
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Ribonucleoproteins
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TATA-Binding Protein Associated Factors
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Transcription Factors
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RNA