Resolution of telomere associations by TRF1 cleavage in mouse embryonic stem cells
Resolution of telomere associations by TRF1 cleavage in mouse embryonic stem cells
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DOI：
10.1091/mbc.e13-10-0564
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发表时间：
2014-07-01
影响因子：
3.3
通讯作者：
Lansdorp, Peter M.
中科院分区：
文献类型：
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作者：
Lisaingo, Kathleen;Uringa, Evert-Jan;Lansdorp, Peter M.
端粒的关联已经在关键的细胞过程如有丝分裂、减数分裂和癌变过程中观察到，并且必须在细胞分裂之前解决以防止基因组不稳定。在这里，我们建立了端粒重复序列结合因子1（TRF 1），端粒蛋白复合物的核心组成部分，是哺乳动物细胞中端粒协会的调解人。使用活细胞成像，我们表明，TRF 1或黄色荧光蛋白（YFP）-TRF 1融合蛋白的表达高于内源性水平，防止在有丝分裂过程中适当的端粒分辨率。TRF 1过表达导致端粒后期桥和含有TRF 1蛋白和端粒DNA的聚集体。烟草蚀纹病毒蛋白酶对YFP-TRF 1的位点特异性蛋白切割可分解端粒聚集体，表明端粒缔合是由TRF 1介导的。这项研究提供了新的见解端粒协会的形成和决议。
Telomere associations have been observed during key cellular processes such as mitosis, meiosis, and carcinogenesis and must be resolved before cell division to prevent genome instability. Here we establish that telomeric repeat-binding factor 1 (TRF1), a core component of the telomere protein complex, is a mediator of telomere associations in mammalian cells. Using live-cell imaging, we show that expression of TRF1 or yellow fluorescent protein (YFP)-TRF1 fusion protein above endogenous levels prevents proper telomere resolution during mitosis. TRF1 overexpression results in telomere anaphase bridges and aggregates containing TRF1 protein and telomeric DNA. Site-specific protein cleavage of YFP-TRF1 by tobacco etch virus protease resolves telomere aggregates, indicating that telomere associations are mediated by TRF1. This study provides novel insight into the formation and resolution of telomere associations.