Structure of the RAD9-RAD1-HUS1 checkpoint clamp bound to RHINO sheds light on the other side of the DNA clamp
Structure of the RAD9-RAD1-HUS1 checkpoint clamp bound to RHINO sheds light on the other side of the DNA clamp
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DOI：
10.1074/jbc.ac119.011816
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发表时间：
2020-01-24
影响因子：
4.8
通讯作者：
Hashimoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Hara, Kodai;Iida, Nao;Hashimoto, Hiroshi
DNA钳是一种高度保守的环状蛋白，在其中心孔内结合双链DNA。此外，DNA钳与其前端的各种核蛋白相互作用，从而刺激它们的酶活性和生物学功能。有人认为DNA钳是从细菌到人类的功能性单面环。在这里，我们报告了与RHINO肽结合的异三聚体RAD 9-RAD 1-HUS 1（9-1-1）检查点钳的晶体结构，RHINO是一种最近发现的癌症相关蛋白，与9-1-1相互作用并促进DNA损伤检查点的激活。这是9-1-1和它的搭档结合的第一个结构。结构揭示了RHINO通过与9 - 1-1的RAD 1亚基的特异性相互作用意外地结合到9 - 1-1环的边缘和背面周围。我们的发现表明，9-1-1是一个功能双面DNA钳。
DNA clamp, a highly conserved ring-shaped protein, binds dsDNA within its central pore. Also, DNA clamp interacts with various nuclear proteins on its front, thereby stimulating their enzymatic activities and biological functions. It has been assumed that the DNA clamp is a functionally single-faced ring from bacteria to humans. Here, we report the crystal structure of the heterotrimeric RAD9-RAD1-HUS1 (9-1-1) checkpoint clamp bound to a peptide of RHINO, a recently identified cancer-related protein that interacts with 9-1-1 and promotes activation of the DNA damage checkpoint. This is the first structure of 9-1-1 bound to its partner. The structure reveals that RHINO is unexpectedly bound to the edge and around the back of the 9-1-1 ring through specific interactions with the RAD1 subunit of 9-1-1. Our finding indicates that 9-1-1 is a functionally double-faced DNA clamp.