Crystal structure and interactions of the Tof1-Csm3 (Timeless-Tipin) fork protection complex
Crystal structure and interactions of the Tof1-Csm3 (Timeless-Tipin) fork protection complex
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DOI：
10.1093/nar/gkaa456
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发表时间：
2020-07-09
影响因子：
14.9
通讯作者：
Grabarczyk, Daniel B.
中科院分区：
文献类型：
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作者：
Grabarczyk, Daniel B.
Tof1-Csm3分叉保护复合体在复制体中起着核心作用——它促进DNA复制分叉的进展，并在它们停滞时保护它们，同时也使内聚建立和检查点反应成为可能。在这里，我以3.1埃的分辨率展示了来自嗜热毛藻的Tof1-Csm3配合物的晶体结构。该结构揭示了两种蛋白质共同形成一个扩展的α螺旋重复结构，这表明该复合物具有机械或脚手架作用。扩展这个想法，我描述了DNA相互作用区域和癌症相关的Mrc1结合位点。这项研究为理解Tof1-Csm3复合物、其人类同源物Timeless- tipin复合物以及果蝇昼夜节律蛋白Timeless的功能提供了分子基础。
The Tof1-Csm3 fork protection complex has a central role in the replisome-it promotes the progression of DNA replication forks and protects themwhen they stall, while also enabling cohesion establishment and checkpoint responses. Here, I present the crystal structure of the Tof1-Csm3 complex from Chaetomium thermophilum at 3.1 angstrom resolution. The structure reveals that both proteins together form an extended alpha helical repeat structure, which suggests a mechanical or scaffolding role for the complex. Expanding on this idea, I characterize a DNA interacting region and a cancer-associated Mrc1 binding site. This study provides the molecular basis for understanding the functions of the Tof1-Csm3 complex, its human orthologue the Timeless-Tipin complex and additionally the Drosophila circadian rhythm protein Timeless.