Mitotic replisome disassembly in vertebrates
Mitotic replisome disassembly in vertebrates
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DOI：
10.1101/418368
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发表时间：
2018-09
期刊：
影响因子：
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通讯作者：
S. Moreno;Rebecca M Jones;Divyasree Poovathumkadavil;Agnieszka Gambus
中科院分区：
文献类型：
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作者：
S. Moreno;Rebecca M Jones;Divyasree Poovathumkadavil;Agnieszka Gambus
近年来，我们对真核生物DNA复制终止过程的理解取得了突破性进展。我们已经表明，在细胞周期的S期DNA复制叉终止时复制机器（复制体）解体的过程是通过复制解旋酶亚基Mcm 7之一的多泛素化驱动的。我们先前在秀丽隐杆线虫胚胎中的工作也表明在有丝分裂中存在复制体解体的备用途径。在这里，我们表明，在非洲爪蟾卵提取物中，任何复制体保留在染色质上的S期后，确实从染色质中有丝分裂。这种有丝分裂解体途径依赖于由TRAIP泛素连接酶和p97/VCP蛋白分离酶的活性在Mcm 7上形成K6和K63泛素链。因此，有丝分裂复制体途径在高等真核生物的进化过程中是保守的。然而，与低等真核生物不同，它不需要SUMO修饰。该过程还可以从染色质中去除任何解旋酶，包括“活性”停滞的解旋酶，这表明该途径的应用比仅用于终止的解旋酶的“备份”广泛得多。
Recent years have brought a breakthrough in our understanding of the process of eukaryotic DNA replication termination. We have shown that the process of replication machinery (replisome) disassembly at the termination of DNA replication forks in S-phase of the cell cycle is driven through polyubiquitylation of one of the replicative helicase subunits Mcm7. Our previous work in C.elegans embryos suggested also an existence of a back-up pathway of replisome disassembly in mitosis. Here we show, that in Xenopus laevis egg extract, any replisome retained on chromatin after S-phase is indeed removed from chromatin in mitosis. This mitotic disassembly pathway depends on formation of K6 and K63 ubiquitin chains on Mcm7 by TRAIP ubiquitin ligase and activity of p97/VCP protein segregase. The mitotic replisome pathway is therefore conserved through evolution in higher eukaryotes. However, unlike in lower eukaryotes it does not require SUMO modifications. This process can also remove any helicases from chromatin, including “active” stalled ones, indicating a much wider application of this pathway than just a “back-up” for terminated helicases.