辐射诱导的常染色质和异染色质焦点的核动态。
Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin.
机构信息
University of Southern California, 1050 Childs Way, Los Angeles, CA, United States.
出版信息
Mutat Res. 2013 Oct;750(1-2):56-66. doi: 10.1016/j.mrfmmm.2013.08.001. Epub 2013 Aug 16.
Abstract
Repair of double strand breaks (DSBs) is essential for cell survival and genome integrity. While much is known about the molecular mechanisms involved in DSB repair and checkpoint activation, the roles of nuclear dynamics of radiation-induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize results from recent studies that point to distinct features of these dynamics in two different chromatin environments: heterochromatin and euchromatin. We also discuss how nuclear architecture and chromatin components might control these dynamics, and the need of novel quantification methods for a better description and interpretation of these phenomena. These studies are expected to provide new biomarkers for radiation risk and new strategies for cancer detection and treatment.
摘要
双链断裂 (DSB) 的修复对于细胞存活和基因组完整性至关重要。虽然人们已经了解了 DSB 修复和检查点激活所涉及的分子机制，但辐射诱导焦点 (RIF) 的核动力学在 DNA 修复中的作用才刚刚开始显现。在这里，我们总结了最近的研究结果，这些结果指出了两种不同染色质环境（异染色质和常染色质）中这些动力学的不同特征。我们还讨论了核结构和染色质成分如何控制这些动力学，以及需要新的定量方法来更好地描述和解释这些现象。这些研究有望为辐射风险提供新的生物标志物，并为癌症检测和治疗提供新的策略。
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1
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2
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Cell. 2013 Mar 14;152(6):1355-64. doi: 10.1016/j.cell.2013.02.010.
3
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4
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5
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7
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10
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