TLS基因敲除小鼠的雄性不育及辐射敏感性增强
Male sterility and enhanced radiation sensitivity in TLS(-/-) mice.
作者信息
Kuroda M, Sok J, Webb L, Baechtold H, Urano F, Yin Y, Chung P, de Rooij D G, Akhmedov A, Ashley T, Ron D
机构信息
Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology and the Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA.
出版信息
EMBO J. 2000 Feb 1;19(3):453-62. doi: 10.1093/emboj/19.3.453.
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.
摘要
TLS（也称为FUS）是一种RNA结合蛋白，它构成了与人类脂肪肉瘤和白血病发生相关的融合癌蛋白的N端一半。我们在此报告，TLS基因发生诱导突变的纯合雄性小鼠不育，减数分裂前精母细胞中未配对和错配的染色体轴数量显著增加。TLS基因敲除小鼠睾丸的核提取物缺乏在体外促进同源DNA序列配对的活性，并且TLS基因敲除小鼠和胚胎成纤维细胞对电离辐射的敏感性增加。这些结果与TLS在同源DNA配对和重组中的作用一致。
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本文引用的文献
1
Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation.人类75千道尔顿DNA配对蛋白与原癌蛋白TLS/FUS相同，且能够促进D环形成。
J Biol Chem. 1999 Nov 26;274(48):34337-42. doi: 10.1074/jbc.274.48.34337.
2
Human POMp75 is identified as the pro-oncoprotein TLS/FUS: both POMp75 and POMp100 DNA homologous pairing activities are associated to cell proliferation.人类POMp75被鉴定为原癌蛋白TLS/FUS：POMp75和POMp100的DNA同源配对活性均与细胞增殖相关。
Oncogene. 1999 Aug 5;18(31):4515-21. doi: 10.1038/sj.onc.1203048.
3
Induction of a secreted protein by the myxoid liposarcoma oncogene.黏液样脂肪肉瘤癌基因诱导分泌蛋白的产生。
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5025-30. doi: 10.1073/pnas.96.9.5025.
4
Oncogenic EWS-Fli1 interacts with hsRPB7, a subunit of human RNA polymerase II.致癌性EWS-Fli1与人类RNA聚合酶II的一个亚基hsRPB7相互作用。
Oncogene. 1998 Aug 6;17(5):603-10. doi: 10.1038/sj.onc.1201964.
5
TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis.TLS/FUS是一种参与多种染色体易位的原癌基因，是BCR/ABL介导的白血病发生的新型调节因子。
EMBO J. 1998 Aug 3;17(15):4442-55. doi: 10.1093/emboj/17.15.4442.
6
Involvement of Brca2 in DNA repair.Brca2参与DNA修复。
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EWS, but not EWS-FLI-1, is associated with both TFIID and RNA polymerase II: interactions between two members of the TET family, EWS and hTAFII68, and subunits of TFIID and RNA polymerase II complexes.EWS而非EWS-FLI-1与TFIID和RNA聚合酶II均相关：TET家族的两个成员EWS和hTAFII68与TFIID和RNA聚合酶II复合物亚基之间的相互作用。
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