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

被引:175
作者
Kuroda, M
Sok, J
Webb, L
Baechtold, H
Urano, F
Yin, Y
Chung, P
de Rooij, DG
Akhmedov, A
Ashley, T
Ron, D [1 ]
机构
[1] NYU, Med Ctr, Skirball Inst Biomol Med, New York, NY 10016 USA
[2] NYU, Med Ctr, Dept Med, New York, NY 10016 USA
[3] NYU, Med Ctr, Dept Cell Biol, New York, NY 10016 USA
[4] NYU, Med Ctr, Kaplan Canc Ctr, New York, NY 10016 USA
[5] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA
[6] Basel Inst Immunol, CH-4005 Basel, Switzerland
[7] Univ Utrecht, Sch Med, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands
关键词
fusion oncoproteins; homologous recombination; spermatogenesis; TLS deficiency;
D O I
10.1093/emboj/19.3.453
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:453 / 462
页数:10
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