In vitro non-homologous DNA end joining assays--the 20th anniversary.

In vitro non-homologous DNA end joining assays--the 20th anniversary.
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DOI:
10.1016/j.biocel.2008.11.007
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发表时间:
2009-06
影响因子:
4
通讯作者:
Winters, Thomas A.
Winters, Thomas A.
中科院分区:
生物学2区
文献类型:
--
作者:
Pastwa, Elzbieta;Somiari, Richard I.;Malinowski, Mariusz;Somiari, Stella B.;Winters, Thomas A.

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DNA双链断裂(DSB)是细胞中最严重的DNA损伤形式。未修复或错误修复的DSB解释了一些遗传不稳定性,导致突变或细胞死亡,从而导致癌症易感性。在人类细胞中,非同源DNA末端连接(NHEJ)是这些断裂的主要修复机制。DNA末端连接研究系统在过去的20年中不断发展。新的测定法与早期的体外DSB修复测定法相比具有一些优势,因为它们耗时较少,允许使用临床材料和检查哺乳动物细胞中生理产生的连接DNA末端。参与NHEJ修复途径的蛋白质可以作为抗癌药物的生物标志物或分子靶点。NHEJ在癌症中的研究结果可以帮助选择有效的修复抑制剂,可以选择性地使肿瘤细胞对电离辐射(IR)和化疗敏感。在这里,我们回顾了体外NHEJ检测的原理和实践,并对这种检测在癌症诊断和治疗中的未来前景提供了一些见解。
DNA double-strand breaks (DSBs) are the most serious forms of DNA damage in cells. Unrepaired or misrepaired DSBs account for some of the genetic instabilities that lead to mutations or cell death, and consequently, to cancer predisposition. In human cells non-homologous DNA end joining (NHEJ) is the main repair mechanism of these breaks. Systems for DNA end joining study have been developing during the last 20 years. New assays have some advantages over earlier in vitro DSBs repair assays because they are less time-consuming, allow the use of clinical material and examination of the joining DNA ends produced physiologically in mammalian cells. Proteins involved in NHEJ repair pathway can serve as biomarkers or molecular targets for anticancer drugs. Results of studies on NHEJ in cancer could help to select potent repair inhibitors that may selectively sensitize tumor cells to ionizing radiation (IR) and chemotherapy. Here, we review the principles and practice of in vitro NHEJ assays and provide some insights into the future prospects of this assay in cancer diagnosis and treatment.
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