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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair.
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The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repair.

机译：SET结构域蛋白Metnase介导外源DNA整合，并将整合链接到非同源末端连接修复。

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摘要

The molecular mechanism by which foreign DNA integrates into the human genome is poorly understood yet critical to many disease processes, including retroviral infection and carcinogenesis, and to gene therapy. We hypothesized that the mechanism of genomic integration may be similar to transposition in lower organisms. We identified a protein, termed Metnase, that has a SET domain and a transposaseuclease domain. Metnase methylates histone H3 lysines 4 and 36, which are associated with open chromatin. Metnase increases resistance to ionizing radiation and increases nonhomologous end-joining repair of DNA doublestrand breaks. Most significantly, Metnase promotes integration of exogenous DNA into the genomes of host cells. Therefore, Metnase is a nonhomologous end-joining repair protein that regulates genomic integration of exogenous DNA and establishes a relationship among histone modification, DNA repair, and integration. The data suggest a model wherein Metnase promotes integration of exogenous DNA by opening chromatin and facilitating joining of DNA ends. This study demonstrates that eukaryotic transposase domains can have important cell functions beyond transposition of genetic elements.
机译：人们很少了解外源DNA整合到人类基因组中的分子机制，但对许多疾病过程（包括逆转录病毒感染和致癌作用）以及基因治疗至关重要。我们假设基因组整合的机制可能类似于低等生物中的转座。我们鉴定了一种蛋白质，称为Metnase，它具有SET结构域和转座酶/核酸酶结构域。 Metnase甲基化与开放染色质相关的组蛋白H3赖氨酸4和36。 Metnase增加了对电离辐射的抵抗力，并增加了DNA双链断裂的非同源末端连接修复。最重要的是，Metnase促进外源DNA整合到宿主细胞的基因组中。因此，Metnase是一种非同源的末端连接修复蛋白，可调节外源DNA的基因组整合并在组蛋白修饰，DNA修复和整合之间建立联系。该数据表明了一种模型，其中Metnase通过打开染色质并促进DNA末端的连接来促进外源DNA的整合。这项研究表明，真核转座酶结构域可以具有重要的细胞功能，而不是遗传成分的转座。

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