The Many Roles of PCNA in Eukaryotic DNA Replication.
The Many Roles of PCNA in Eukaryotic DNA Replication.
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DOI：
10.1016/bs.enz.2016.03.003
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Washington MT
中科院分区：
文献类型：
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作者：
Boehm EM;Gildenberg MS;Washington MT
增殖细胞核抗原（PCNA）在DNA复制和复制相关过程的许多方面起着关键作用，包括跨损伤合成、无错误损伤旁路、断裂诱导复制、错配修复和染色质组装。自发现以来，我们对PCNA的看法已经从复制辅助因子演变为大型蛋白质-蛋白质相互作用网络中的中心蛋白质，该网络组织和协调复制叉处的许多关键事件。我们开始这篇评论文章的结构和功能的PCNA的概述。我们讨论了它的许多相互作用的合作伙伴结合的方式，以及这些相互作用是如何调节的翻译后修饰，如泛素化和sumoylation。然后，我们探讨了PCNA在正常DNA复制和复制偶联DNA损伤耐受和修复过程中的许多作用。我们的结论是考虑如何PCNA可以与这么多的结合伙伴进行物理相互作用，以执行其众多的角色。我们认为，有一个大的，动态的网络连接的PCNA分子在复制叉和周围。这个网络将有助于增加DNA复制和复制相关过程所需的所有蛋白质的局部浓度，并调节它们的各种活动。
Proliferating cell nuclear antigen (PCNA) plays critical roles in many aspects of DNA replication and replication-associated processes, including translesion synthesis, error-free damage bypass, break-induced replication, mismatch repair, and chromatin assembly. Since its discovery, our view of PCNA has evolved from a replication accessory factor to the hub protein in a large protein-protein interaction network that organizes and orchestrates many of the key events at the replication fork. We begin this review article with an overview of the structure and function of PCNA. We discuss the ways its many interacting partners bind and how these interactions are regulated by post-translational modifications such as ubiquitylation and sumoylation. We then explore the many roles of PCNA in normal DNA replication and in replication-coupled DNA damage tolerance and repair processes. We conclude by considering how PCNA can interact physically with so many binding partners to carry out its numerous roles. We propose that there is a large, dynamic network of linked PCNA molecules at and around the replication fork. This network would serve to increase the local concentration of all the proteins necessary for DNA replication and replication-associated processes and to regulate their various activities.