The p97 segregase cofactor Ubxn7 facilitates replisome disassembly during S-phase.
The p97 segregase cofactor Ubxn7 facilitates replisome disassembly during S-phase.
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DOI：
10.1016/j.jbc.2022.102234
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发表时间：
2022-08
影响因子：
4.8
通讯作者：
Gambus, Agnieszka
中科院分区：
文献类型：
--
作者：
Tarcan, Zeynep;Poovathumkadavil, Divyasree;Skagia, Aggeliki;Gambus, Agnieszka
复杂的细胞过程是由大型多蛋白复合物的调节组装和拆卸驱动的。虽然我们已经开始了解真核生物DNA复制机制（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。最近，这个过程的第一个元素已经出现，揭示了复制解旋酶，在复制体的心脏，是多泛素化之前卸载，这种卸载需要p97分离酶活性。两种不同的E3泛素连接酶现在已经显示在不同条件下泛素化解旋酶：Cul2Lrr1和TRAIP。在这里，我们使用非洲爪蟾卵提取物无细胞系统和生化方法，发现了两种p97辅因子Ubxn 7和Faf 1，它们可以在S期复制体解体过程中与p97相互作用。然而，我们仅显示Ubxn7促进了有效的复制体拆卸。Ubxn 7通过其与Cul2Lrr1和p97的独立结构域相互作用来实现这一作用，以允许Mcm7泛素化和其从染色质中去除之间的偶联。因此，我们的数据表征Ubxn 7作为第一个底物特异性p97辅因子调节脊椎动物中的复制体解体和Cul2Lrr1复制体卸载途径在未受干扰的S期的功效的理由。
Complex cellular processes are driven by the regulated assembly and disassembly of large multiprotein complexes. While we are beginning to understand the molecular mechanism for assembly of the eukaryotic DNA replication machinery (replisome), we still know relatively little about the regulation of its disassembly at replication termination. Recently, 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 have now been shown to ubiquitylate the helicase under different conditions: Cul2Lrr1 and TRAIP. Here, using Xenopus laevis egg extract cell-free system and biochemical approaches, we have found two p97 cofactors, Ubxn7 and Faf1, which can interact with p97 during replisome disassembly during S-phase. We show only Ubxn7, however, facilitates efficient replisome disassembly. Ubxn7 delivers this role through its interaction via independent domains with both Cul2Lrr1 and p97 to allow coupling between Mcm7 ubiquitylation and its removal from chromatin. Our data therefore characterize Ubxn7 as the first substrate-specific p97 cofactor regulating replisome disassembly in vertebrates and a rationale for the efficacy of the Cul2Lrr1 replisome unloading pathway in unperturbed S-phase.
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影响因子：
4.8
作者：
Gillespie, Peter J.;Gambus, Agnieszka;Blow, J. Julian
通讯作者：
Blow, J. Julian
DOI：
10.1083/jcb.202009147
发表时间：
2021-08-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fan Y;Köberlin MS;Ratnayeke N;Liu C;Deshpande M;Gerhardt J;Meyer T
通讯作者：
Meyer T
影响因子：
16.6
作者：
Franz A;Pirson PA;Pilger D;Halder S;Achuthankutty D;Kashkar H;Ramadan K;Hoppe T
通讯作者：
Hoppe T
影响因子：
21.3
作者：
Gambus, A;Jones, RC;Labib, K
通讯作者：
Labib, K
影响因子：
10.5
作者：
Dewar JM;Low E;Mann M;Räschle M;Walter JC
通讯作者：
Walter JC