Shelterin Protects Chromosome Ends by Compacting Telomeric Chromatin.
Shelterin Protects Chromosome Ends by Compacting Telomeric Chromatin.
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DOI：
10.1016/j.cell.2016.01.036
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发表时间：
2016-02-11
期刊：
影响因子：
64.5
通讯作者：
Yildiz A
中科院分区：
文献类型：
--
作者：
Bandaria JN;Qin P;Berk V;Chu S;Yildiz A
端粒是位于染色体末端的重复DNA序列，通过保护素复合体来防御DNA损伤反应(DDR)。为了了解保护素如何保护端粒末端，我们使用超分辨率显微镜研究了人类细胞中端粒染色质的结构组织。我们发现，端粒形成紧密的球状结构是通过端粒和端粒DNA之间相互作用的复杂网络，而不是通过端粒和亚端粒区域的DNA甲基化、组蛋白去乙酰化或组蛋白三甲基化。破坏掩蔽性组装或从端粒中移除个别亚基的突变会导致端粒体积增加10倍。解压后的端粒更容易被端粒相关蛋白结合，并积累DDR信号。用正交法重新结合端粒染色质，取代端粒上的DDR信号。这些结果揭示了Shelterin的染色质重塑活性，并表明Shelterin介导的端粒染色质紧致为染色体末端提供了强大的保护，使其免受DDR机制的影响。
Telomeres, repetitive DNA sequences at chromosome ends, are shielded against the DNA damage response (DDR) by the shelterin complex. To understand how shelterin protects telomere ends, we investigated the structural organization of telomeric chromatin in human cells using super-resolution microscopy. We found that telomeres form compact globular structures through a complex network of interactions between shelterin subunits and telomeric DNA, and not by DNA methylation, histone deacetylation or histone trimethylation at telomeres and subtelomeric regions. Mutations that abrogate shelterin assembly or removal of individual subunits from telomeres cause up to a 10-fold increase in telomere volume. Decompacted telomeres become more accessible to telomere-associated proteins and accumulate DDR signals. Recompaction of telomeric chromatin using an orthogonal method displaces DDR signals from telomeres. These results reveal the chromatin remodeling activity of shelterin and demonstrate that shelterin-mediated compaction of telomeric chromatin provides robust protection of chromosome ends against the DDR machinery.