Processing of DNA damage clusters in human cells: current status of knowledge
Processing of DNA damage clusters in human cells: current status of knowledge
复制标题
DOI：
10.1039/b713178j
复制
发表时间：
2008-01-01
影响因子：
--
通讯作者：
Georgakilas, Alexandros G.
中科院分区：
文献类型：
--
作者：
Georgakilas, Alexandros G.
暴露于DNA损伤剂的真核细胞通过诱导参与DNA修复、细胞周期检查点控制和潜在凋亡的多种蛋白质激活重要的防御途径。在接受了即使是低剂量的电离辐射甚至是内源性也可以诱导氧化产生的聚集性DNA损伤（OCDL：紧密间隔的DNA损伤）的假设之后，在对紧密间隔DNA损伤修复的生物化学基础的理解方面取得了重大进展，许多问题仍然没有得到解答。在不久的将来，必须回答的主要问题是：1)如果人类细胞修复这些类型的DNA损伤，它们是如何处理的；2)在处理两个紧密间隔的DNA损伤过程中，在什么条件下会产生双链断裂（DSB）； 3)什么类型的修复蛋白相互作用控制着复杂DNA损伤的处理？到目前为止，关于人体细胞和组织的现有数据非常有限，而且在某些情况下相互矛盾。然而，他们都同意，获得细胞用来对抗和处理位于小DNA体积内的复杂DNA损伤的途径的机制见解非常重要，并且需要进行更深入的分析研究。我们选择性地回顾了最近获得的关于人类细胞和组织中非dsb DNA损伤簇处理的数据，并讨论了该领域知识的现状。
Eukaryotic cells exposed to DNA damaging agents activate important defensive pathways by inducing multiple proteins involved in DNA repair, cell cycle checkpoint control and potentially apoptosis. After the acceptance of the hypothesis that oxidatively generated clustered DNA lesions (OCDL: closely spaced DNA lesions) can be induced even by low doses of ionizing radiation or even endogenously, and significant advances have been made in the understanding of the biochemistry underlying the repair of closely spaced DNA lesions, many questions still remain unanswered. The major questions that have to be answered in the near future are: 1) how human cells process these types of DNA damage if they repair them at all, 2) under what conditions a double strand break (DSB) may be created during the processing of two closely spaced DNA lesions and 3) what type of repair protein interactions govern the processing of complex DNA damage? The data existing so far on human cells and tissues are very limited and in some cases contradicting. All of them though agree however on the major importance of gaining mechanistic insights on the pathways used by the cell to confront and process complex DNA damage located in a small DNA volume and the need of more in depth analytical studies. We selectively review recently-obtained data on the processing of non-DSB DNA damage clusters in human cells and tissues and discuss the current status of knowledge in the field.