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首页> 外文期刊>Nature >SEQUENCE-SPECIFIC DNA BINDING BY KU AUTOANTIGEN AND ITS EFFECTS ON TRANSCRIPTION
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SEQUENCE-SPECIFIC DNA BINDING BY KU AUTOANTIGEN AND ITS EFFECTS ON TRANSCRIPTION

机译：KU自身抗原对特定序列DNA的结合及其对转录的影响

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摘要

DNA-DEPENDENT protein kinase (DNA-PK) has been implicated in several nuclear processes including transcription(1-3), DNA replication(4,5), double-stranded DNA break repair, and V(D)J recom bination(6-10). Linkage of kinase and substrate on DNA in cis is required for efficient phosphorylation(11). Recruitment of DNA-PK to DNA is by Ku autoantigen, a DNA-end-binding protein required for DNA-PK catalytic activity(11). Although Ku is known to translocate along naked DNA(12), how DNA-end binding by Ku might lead to DNA-PK-mediated phosphorylation of sequence-specific DNA-binding proteins in vivo has not been obvious. Here we report the identification of Ku as a transcription factor that recruits DNA-PK directly to specific DNA sequences. NRE1 (negative regulatory element 1) is a DNA sequence element (-394/ - 381) in the long terminal repeat of mouse mammary tumour virus (MMTV) that is important for repressing inappropriate viral expression(13-16). We show that direct binding of Ku/DNA-PK to NRE1 represses glucocorticoid-induced MMTV transcription. [References: 28]
机译：DNA-DEPENDENT蛋白激酶（DNA-PK）与转录（1-3），DNA复制（4,5），双链DNA断裂修复和V（D）J重组（6）的几个核过程有关（6） -10）。激酶与顺式DNA底物的连接是有效磷酸化所必需的（11）。从DNA PK到DNA的吸收是通过Ku自身抗原进行的，Ku自身抗原是DNA-PK催化活性所需的DNA末端结合蛋白（11）。尽管已知Ku会沿着裸露的DNA转运（12），但Ku的DNA末端结合如何在体内导致DNA-PK介导的序列特异性DNA结合蛋白的磷酸化尚不清楚。在这里，我们报告鉴定Ku作为转录因子，其直接将DNA-PK募集到特定的DNA序列。 NRE1（负调控元件1）是小鼠乳腺肿瘤病毒（MMTV）的长末端重复序列中的DNA序列元件（-394 /-381），对于抑制不适当的病毒表达非常重要（13-16）。我们表明Ku / DNA-PK到NRE1的直接结合抑制了糖皮质激素诱导的MMTV转录。 [参考：28]

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