Stop pulling my strings - what telomeres taught us about the DNA damage response.
Stop pulling my strings - what telomeres taught us about the DNA damage response.
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DOI：
10.1038/nrm.2016.43
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Sfeir A
中科院分区：
文献类型：
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作者：
Lazzerini-Denchi E;Sfeir A
哺乳动物细胞已经进化出专门的机制来感知和修复双链断裂（DSB）以维持基因组稳定性。然而，在某些情况下，这些途径的活性可导致异常的DNA修复、基因组不稳定性和肿瘤发生。其中一个例子是线性染色体自然末端的DNA修复，称为端粒，这可能导致染色体末端融合。在这里，我们回顾了过去十年中获得的数据，并讨论了保护哺乳动物染色体末端免受DNA损伤反应的机制。我们还讨论了端粒研究如何帮助发现DSB修复的关键步骤。最后，我们总结了功能失调的端粒和随之而来的基因组不稳定性如何驱动癌症的进展。
Mammalian cells have evolved specialized mechanisms to sense and repair double-strand breaks (DSBs) to maintain genomic stability. However, in certain cases, the activity of these pathways can lead to aberrant DNA repair, genomic instability and tumorigenesis. One such case is DNA repair at the natural ends of linear chromosomes, known as telomeres, which can lead to chromosome-end fusions. Here, we review data obtained over the past decade and discuss the mechanisms that protect mammalian chromosome ends from the DNA damage response. We also discuss how telomere research has helped to uncover key steps in DSB repair. Last, we summarize how dysfunctional telomeres and the ensuing genomic instability drive the progression of cancer.