Male sterility and enhanced radiation sensitivity in TLS-/- mice
Male sterility and enhanced radiation sensitivity in TLS-/- mice
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DOI：
10.1093/emboj/19.3.453
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发表时间：
2000-02-01
期刊：
影响因子：
11.4
通讯作者：
Ron, D
中科院分区：
文献类型：
--
作者：
Kuroda, M;Sok, J;Ron, D
TLS（也称为FUS）是一种RNA结合蛋白，其贡献了与人类脂肪肉瘤和白血病的发展有关的融合癌蛋白的N-末端一半。在此，我们报告了TLS诱导突变的纯合子雄性小鼠不育，减数分裂前精母细胞中未配对和错配对的染色体轴数量显著增加。TLS-/-睾丸的核提取物缺乏能够促进体外同源DNA序列之间配对的活性，TLS-/-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。
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.