Multiple pathways inhibit NHEJ at telomeres
Multiple pathways inhibit NHEJ at telomeres
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DOI：
10.1101/gad.455108
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发表时间：
2008-05-01
影响因子：
10.5
通讯作者：
Callebaut, Isabelle
中科院分区：
文献类型：
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作者：
Marcand, Stephane;Pardo, Benjamin;Callebaut, Isabelle
非同源末端连接（NHEJ）修复途径在端粒被抑制，阻止染色体融合。在出芽酵母（Saccharomyces cerevisiae）中，Rap1蛋白直接结合端粒序列，是抑制NHEJ所必需的。在这里，我们发现Rap1 c端结构域通过蛋白Rif2和Sir4建立了两条平行的抑制途径。此外，Rap1的中心结构域独立于Rif2和Sir4抑制NHEJ。因此，Rap1建立了几个独立的途径来阻止端粒融合。我们讨论了一种可能的机制，可以解释Rif2在端粒上的多功能性，以及Rif2最近从起源识别复合体（ORC）亚基进化起源。
The nonhomologous end-joining (NHEJ) repair pathway is inhibited at telomeres, preventing chromosome fusion. In budding yeast Saccharomyces cerevisiae, the Rap1 protein directly binds the telomere sequences and is required for NHEJ inhibition. Here we show that the Rap1 C-terminal domain establishes two parallel inhibitory pathways through the proteins Rif2 and Sir4. In addition, the central domain of Rap1 inhibits NHEJ independently of Rif2 and Sir4. Thus, Rap1 establishes several independent pathways to prevent telomere fusions. We discuss a possible mechanism that would explain Rif2 multifunctionality at telomeres and the recent evolutionary origin of Rif2 from an origin recognition complex (ORC) subunit.