The PIAS homologue Siz2 regulates perinuclear telomere position and telomerase activity in budding yeast
The PIAS homologue Siz2 regulates perinuclear telomere position and telomerase activity in budding yeast
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DOI：
10.1038/ncb2263
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发表时间：
2011-07-01
影响因子：
21.3
通讯作者：
Gasser, Susan M.
中科院分区：
文献类型：
--
作者：
Ferreira, Helder C.;Luke, Brian;Gasser, Susan M.
出芽酵母端粒通过两个部分冗余的途径可逆地结合在核膜上，这两个途径包括Sir2/3/4沉默复合体和Yku70/80异源二聚体（1,2）。为了更好地理解这是如何调节的，我们研究了sumo化在端粒锚定中的作用。我们发现类似pias的SUMO E3连接酶Siz2在体内可以介导Yku70/80和Sir4，并促进端粒锚定在核膜上。值得注意的是，Siz2的缺失也会以端粒酶依赖的方式引发端粒延伸，这种方式与解旋酶Pif1的缺失是上位性的。与我们之前记录的端粒酶在锚定中的作用一致(3)，PIF1缺失可以恢复正常的端粒锚定在siz2 Delta中。通过一个极短的端粒的活细胞成像，我们表明端粒在拉长时从核包膜转移了一种方式。我们认为sumo依赖于核外周的关联抑制了结合的端粒酶，而活性延伸与端粒释放相关。
Budding yeast telomeres are reversibly bound at the nuclear envelope through two partially redundant pathways that involve the Sir2/3/4 silencing complex and the Yku70/80 heterodimer(1,2). To better understand how this is regulated, we studied the role of SUMOylation in telomere anchoring. We find that the PIAS-like SUMO E3 ligase Siz2 sumoylates both Yku70/80 and Sir4 in vivo and promotes telomere anchoring to the nuclear envelope. Remarkably, loss of Siz2 also provokes telomere extension in a telomerase-dependent manner that is epistatic with loss of the helicase Pif1. Consistent with our previously documented role for telomerase in anchorage(3), normal telomere anchoring in siz2 Delta is restored by PIF1 deletion. By live-cell imaging of a critically short telomere, we show that telomeres shift a way from the nuclear envelope when elongating. We propose that SUMO-dependent association with the nuclear periphery restrains bound telomerase, whereas active elongation correlates with telomere release.