PCNA on the crossroad of cancer
PCNA on the crossroad of cancer
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DOI：
10.1042/bst0370605
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发表时间：
2009-06-01
影响因子：
3.9
通讯作者：
Helleday, Thomas
中科院分区：
文献类型：
--
作者：
Stolimenov, Ivaylo;Helleday, Thomas
癌症是由基因变化引起的，这些变化通常是由于未能准确复制DNA而引起的。增殖细胞核抗原(增殖细胞核抗原)在DNA周围形成一个环，以促进和控制DNA复制。越来越多的证据表明，增殖细胞核抗原是许多重要的细胞过程的核心，如DNA复制、DNA损伤修复、染色质结构维持、染色体分离和细胞周期进程。DNA复制分叉的进展可以被DNA损伤阻止，DNA损伤要么是由内源性损伤形成的，要么是由外源性因素形成的，例如抗癌药物。细胞反应经常导致由特定的翻译后修饰(即泛素化)或通过交换其相互作用伙伴而触发的增殖细胞核抗原功能的改变。这使增殖细胞核抗原在决定复制分叉命运的过程中处于核心地位。在这篇文章中，我们回顾了增殖细胞核抗原的修饰和相互作用伙伴，以及这些如何影响复制叉处的事件过程，最终决定了肿瘤的进展和抗癌治疗的结果。
Cancer is caused by genetic changes that often arise following failure to accurately replicate the DNA. PCNA (proliferating-cell nuclear antigen) forms a ring around the DNA to facilitate and control DNA replication. Emerging evidence suggests that PCNA is at the very heart of many essential cellular processes, such as DNA replication, repair of DNA damage, chromatin structure maintenance, chromosome segregation and cell-cycle progression. Progression of the DNA replication forks can be blocked by DNA lesions, formed either by endogenous damage or by exogenous agents, for instance anticancer drugs. cellular response often results in change of PCNA function triggered either by specific post-translational modification of PCNA (i.e. ubiquitylation) or by exchange of its interaction partners. This puts PCNA in a central position in determining the fate of the replication fork. in the present article, we review PCNA modifications and interaction partners, and how those influence the course of events at replication forks, which ultimately determines both tumour progression as well as the outcome of anticancer treatment.