Esc2 promotes Mus81 complex-activity via its SUMO-like and DNA binding domains.
Esc2 promotes Mus81 complex-activity via its SUMO-like and DNA binding domains.
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DOI：
10.1093/nar/gkw882
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发表时间：
2017-01-09
影响因子：
14.9
通讯作者：
Krejci L
中科院分区：
文献类型：
--
作者：
Sebesta M;Urulangodi M;Stefanovie B;Szakal B;Pacesa M;Lisby M;Branzei D;Krejci L
跨受损DNA模板的复制伴随着姐妹染色单体连接（SCJ）的瞬时形成。缺乏Esc 2的细胞，一种不含已知酶结构域的衔接蛋白，在这些SCJ的代谢中有缺陷。然而，Esc 2如何参与SCJ的代谢仍然是难以捉摸的。在这里，我们显示Esc 2和结构特异性内切核酸酶Mus 81-Mms 4（Mus 81复合物）之间的相互作用，它们参与SCJs的代谢，以及Esc 2对Mus 81复合物的酶活性的影响。我们发现Esc 2通过其SUMO样结构域与Mus 81复合物特异性相互作用，在体外刺激Mus 81复合物的酶活性，并参与体内SCJ的Mus 81复合物依赖性分辨率。总的来说，我们的数据表明，Esc 2参与SCJ代谢的可能性部分是通过调节Mus 81复合物的活性。
Replication across damaged DNA templates is accompanied by transient formation of sister chromatid junctions (SCJs). Cells lacking Esc2, an adaptor protein containing no known enzymatic domains, are defective in the metabolism of these SCJs. However, how Esc2 is involved in the metabolism of SCJs remains elusive. Here we show interaction between Esc2 and a structure-specific endonuclease Mus81-Mms4 (the Mus81 complex), their involvement in the metabolism of SCJs, and the effects Esc2 has on the enzymatic activity of the Mus81 complex. We found that Esc2 specifically interacts with the Mus81 complex via its SUMO-like domains, stimulates enzymatic activity of the Mus81 complex in vitro, and is involved in the Mus81 complex-dependent resolution of SCJs in vivo. Collectively, our data point to the possibility that the involvement of Esc2 in the metabolism of SCJs is, in part, via modulation of the activity of the Mus81 complex.