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

Masahiko Kuroda; John Sok; Lisa Webb; Heidi Baechtold; Fumihiko Urano; Yin Yin; Peter Chung; Dirk G. De Rooij; Alexandre Akhmedov; Terry Ashley; David Ron

doi:10.1093/emboj/19.3.453

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

Masahiko Kuroda, John Sok, Lisa Webb, Heidi Baechtold, Fumihiko Urano, Yin Yin, Peter Chung, Dirk G. De Rooij, Alexandre Akhmedov, Terry Ashley, David Ron

Research output: Contribution to journal › Article › peer-review

175 Scopus citations

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 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.

Original language	English
Pages (from-to)	453-462
Number of pages	10
Journal	EMBO Journal
Volume	19
Issue number	3
DOIs	https://doi.org/10.1093/emboj/19.3.453
State	Published - Feb 1 2000

Keywords

Fusion oncoproteins
Homologous recombination
Spermatogenesis
TLS deficiency

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10.1093/emboj/19.3.453

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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 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.",

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T1 - Male sterility and enhanced radiation sensitivity in TLS(-/-) mice

AU - Kuroda, Masahiko

AU - Sok, John

AU - Webb, Lisa

AU - Baechtold, Heidi

AU - Urano, Fumihiko

AU - Yin, Yin

AU - Chung, Peter

AU - De Rooij, Dirk G.

AU - Akhmedov, Alexandre

AU - Ashley, Terry

AU - Ron, David

PY - 2000/2/1

Y1 - 2000/2/1

N2 - 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.

AB - 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.

KW - Fusion oncoproteins

KW - Homologous recombination

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KW - TLS deficiency

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JO - EMBO Journal

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

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