End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1
End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1
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DOI：
10.1038/emboj.2013.24
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发表时间：
2013-03-20
期刊：
影响因子：
11.4
通讯作者：
Marcand, Stephane
中科院分区：
文献类型：
--
作者：
Lescasse, Rachel;Pobiega, Sabrina;Marcand, Stephane
在真核生物中，永久抑制端粒的非同源末端连接（NHEJ）修复途径可确保染色体末端不融合。在出芽酵母中，Rap1与端粒重复序列的结合建立了NHEJ抑制。在这里，我们证明Uls1蛋白是维持端粒NHEJ抑制所必需的。Uls1蛋白是一种非必需的Swi2/ snf2相关转位酶，也是一种靶向未知靶点的小泛素相关修饰物（SUMO）靶向泛素连接酶（STUbL）。Uls1缺失导致端粒-端粒融合。由于缺乏多聚sumo链和rap1等位基因缺乏sumo化位点，对Uls1的需求减轻。此外，Uls1限制了Rap1 poly-SUMO偶联物的积累。我们认为Uls1的功能之一是清除端粒中无功能的多sumoylated Rap1分子，以确保NHEJ抑制的持续效率。由于Uls1是已知的唯一具有转位酶活性的STUbL，它可以作为清除真核生物DNA上多sumoylated蛋白的一般分子清道夫。EMBO杂志（2013）32,805-815。doi: 10.1038 / emboj.2013.24;2013年2月15日在线发布
In eukaryotes, permanent inhibition of the non-homologous end joining (NHEJ) repair pathway at telomeres ensures that chromosome ends do not fuse. In budding yeast, binding of Rap1 to telomere repeats establishes NHEJ inhibition. Here, we show that the Uls1 protein is required for the maintenance of NHEJ inhibition at telomeres. Uls1 protein is a non-essential Swi2/Snf2-related translocase and a Small Ubiquitin-related Modifier (SUMO)-Targeted Ubiquitin Ligase (STUbL) with unknown targets. Loss of Uls1 results in telomere-telomere fusions. Uls1 requirement is alleviated by the absence of poly-SUMO chains and by rap1 alleles lacking SUMOylation sites. Furthermore, Uls1 limits the accumulation of Rap1 poly-SUMO conjugates. We propose that one of Uls1 functions is to clear non-functional poly-SUMOylated Rap1 molecules from telomeres to ensure the continuous efficiency of NHEJ inhibition. Since Uls1 is the only known STUbL with a translocase activity, it can be the general molecular sweeper for the clearance of poly-SUMOylated proteins on DNA in eukaryotes. The EMBO Journal (2013) 32, 805-815. doi:10.1038/emboj.2013.24; Published online 15 February 2013