Mechanism of cluster DNA damage repair in response to high-atomic number and energy particles radiation.
Mechanism of cluster DNA damage repair in response to high-atomic number and energy particles radiation.
复制标题
群集DNA损伤修复的机理，响应高原子数和能量颗粒辐射。
DOI：
10.1016/j.mrfmmm.2010.11.002
复制
发表时间：
2011-06-03
影响因子：
2.3
通讯作者：
Chen, David J.
中科院分区：
文献类型：
--
作者：
Asaithamby, Aroumougame;Chen, David J.
低线能量转移(LET)辐射(即γ和X射线)导致DNA双链断裂(DSB)，并迅速修复(重新连接)。相比之下，高原子序数和能量(HZE)粒子的致密电离轨迹造成的DNA损伤是缓慢修复或无法修复的。这些未修复和/或错误修复的DNA损伤可能有助于在HZE粒子照射的细胞中观察到比低LET辐射处理的细胞具有更高的细胞杀伤、染色体畸变、诱变和致癌的相对生物学效率。HZE颗粒诱导的DNA损伤类型在体外已有特征，通常由两个或更多紧密间隔的链断裂、碱性位点或相反链上的氧化碱基组成。目前尚不清楚这些损伤难以修复的原因。在这篇综述中，我们强调了一种新技术的潜力，该技术可以直接显示人类细胞中不同类型的DNA损伤，并证明了活细胞成像对于阐明复杂DNA损伤的时空特征的新意义。我们重点介绍了参与HZE颗粒诱导的DSB修复的分子途径的最新见解。我们还讨论了我们在理解不同的末端加工核酸酶如何帮助修复由HZE颗粒产生的复杂末端的DSB方面的最新进展。了解HZE颗粒引起DNA损伤修复的机制，对于估计HZE颗粒暴露对人类健康的风险具有重要意义。
Low-linear energy transfer (LET) radiation (i.e., γ- and X-rays) induces DNA double-strand breaks (DSBs) that are rapidly repaired (rejoined). In contrast, DNA damage induced by the dense ionizing track of high-atomic number and energy (HZE) particles are slowly repaired or are irreparable. These unrepaired and/or misrepaired DNA lesions may contribute to the observed higher relative biological effectiveness for cell killing, chromosomal aberrations, mutagenesis, and carcinogenesis in HZE particle irradiated cells compared to those treated with low-LET radiation. The types of DNA lesions induced by HZE particles have been characterized in vitro and usually consist of two or more closely spaced strand breaks, abasic sites, or oxidized bases on opposing strands. It is unclear why these lesions are difficult to repair. In this review, we highlight the potential of a new technology allowing direct visualization of different types of DNA lesions in human cells and document the emerging significance of live-cell imaging for elucidation of the spatio-temporal characterization of complex DNA damage. We focus on the recent insights into the molecular pathways that participate in the repair of HZE particle-induced DSBs. We also discuss recent advances in our understanding of how different end-processing nucleases aid in repair of DSBs with complicated ends generated by HZE particles. Understanding the mechanism underlying the repair of DNA damage induced by HZE particles will have important implications for estimating the risks to human health associated with HZE particle exposure.
登录
查看更多内容
DOI：
10.1073/pnas.131077798
发表时间：
2001-06-19
影响因子：
11.1
作者：
Blaisdell, JO;Wallace, SS
通讯作者：
Wallace, SS
DOI：
10.1073/pnas.052545899
发表时间：
2002-03-19
影响因子：
11.1
作者：
Allen, C;Kurimasa, A;Nickoloff, JA
通讯作者：
Nickoloff, JA
影响因子：
4.8
作者：
Baynton, K;Otterlei, M;Seeberg, E
通讯作者：
Seeberg, E
影响因子：
7.7
作者：
Constantinou, A;Tarsounas, M;West, SC
通讯作者：
West, SC
影响因子：
4.3
作者：
Costes, Sylvain V.;Ponomarev, Artem;Chen, James L.;Nguyen, David;Cucinotta, Francis A.;Barcellos-Hoff, Mary Helen
通讯作者：
Barcellos-Hoff, Mary Helen