Termination of DNA replication forks: "Breaking up is hard to do".
Termination of DNA replication forks: "Breaking up is hard to do".
复制标题
DNA复制叉的终止：“分手很难做到”。
DOI：
10.1080/19491034.2015.1035843
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Gambus A
中科院分区：
文献类型：
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作者：
Bailey R;Priego Moreno S;Gambus A
为了确保整个基因组的复制，真核DNA复制从数千个复制起点开始。复制叉穿过染色质，直到它们遇到来自相邻起点的叉。在复制叉终止叉会聚期间，复制体分解并且拓扑异构酶II分解子DNA分子。如果不能有效地解决，终止叉通过形成致病结构导致基因组不稳定。我们最近的发现揭示了复制叉终止后复制体解体的机制。我们已经证明，复制性解旋酶组分-Mcm 7的终止特异性聚遍在化会导致活性解旋酶在依赖于p97/VCP/Cdc 48分离酶的过程中溶解。终止解旋酶分解的抑制导致复制终止缺陷。在这个扩展的视图中，我们提出了假设的复制叉终止模型，并讨论在DNA复制终止领域的剩余和新出现的问题。
To ensure duplication of the entire genome, eukaryotic DNA replication initiates from thousands of replication origins. The replication forks move through the chromatin until they encounter forks from neighboring origins. During replication fork termination forks converge, the replisomes disassemble and topoisomerase II resolves the daughter DNA molecules. If not resolved efficiently, terminating forks result in genomic instability through the formation of pathogenic structures. Our recent findings shed light onto the mechanism of replisome disassembly upon replication fork termination. We have shown that termination-specific polyubiquitylation of the replicative helicase component – Mcm7, leads to dissolution of the active helicase in a process dependent on the p97/VCP/Cdc48 segregase. The inhibition of terminating helicase disassembly resulted in a replication termination defect. In this extended view we present hypothetical models of replication fork termination and discuss remaining and emerging questions in the DNA replication termination field.