The p97 cofactor Ubxn7 facilitates replisome disassembly during S-phase
The p97 cofactor Ubxn7 facilitates replisome disassembly during S-phase
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p97 辅因子 Ubxn7 促进 S 期复制体分解
DOI：
10.1101/2021.12.16.472925
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Tarcan Z
中科院分区：
文献类型：
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作者：
Tarcan Z
复杂的细胞过程由大型多蛋白质复合物的调节组装和拆卸驱动。在真核DNA复制中，虽然我们开始了解复制机器（复制体）组装的分子机制，但我们对复制终止时复制体解体的调控仍然知之甚少。近年来，这一过程的第一个要素已经出现，揭示了复制体核心的复制解旋酶在卸载之前被聚遍在蛋白质，并且这种卸载需要p97分离酶活性。现在已知两种不同的E3泛素连接酶在不同条件下使解旋酶泛素化：Cul2Lrr1和TRAIP。在这里，我们发现了两个p97辅因子Ubxn 7和Faf 1，它们可以在S期的复制体解体过程中与p97相互作用。然而，只有Ubxn 7通过与Cul2Lrr1和p97的相互作用促进有效的复制体解体。因此，我们的数据证明Ubxn 7是脊椎动物中第一个调节复制体分解的底物特异性p97辅因子。
Complex cellular processes are driven by the regulated assembly and disassembly of large multi-protein complexes. In eukaryotic DNA replication, whilst we are beginning to understand the molecular mechanism for assembly of the replication machinery (replisome), we still know relatively little about the regulation of its disassembly at replication termination. Over recent years, the first elements of this process have emerged, revealing that the replicative helicase, at the heart of the replisome, is polyubiquitylated prior to unloading and that this unloading requires p97 segregase activity. Two different E3 ubiquitin ligases are now known to ubiquitylate the helicase under different conditions: Cul2Lrr1and TRAIP. Here we have found two p97 cofactors, Ubxn7 and Faf1, which can interact with p97 during replisome disassembly in S-phase. Only Ubxn7 however facilitates efficient replisome disassembly through its interaction with both Cul2Lrr1and p97. Our data therefore characterise Ubxn7 as the first substrate-specific p97 cofactor regulating replisome disassembly in vertebrates.