Acetylation of the SUN protein Mps3 by Eco1 regulates its function in nuclear organization.
Acetylation of the SUN protein Mps3 by Eco1 regulates its function in nuclear organization.
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DOI：
10.1091/mbc.e11-07-0600
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发表时间：
2012-07
影响因子：
3.3
通讯作者：
Jaspersen SL
中科院分区：
文献类型：
--
作者：
Ghosh S;Gardner JM;Smoyer CJ;Friederichs JM;Unruh JR;Slaughter BD;Alexander R;Chisholm RD;Lee KK;Workman JL;Jaspersen SL
SUN蛋白Mps3被Eco1乙酰化，调节核组织，包括染色体凝聚、端粒拴系和基因沉默，而不影响Mps3在核膜上的分布。它是已知的影响细胞核内染色体定位的调节途径之一。酿酒酵母太阳域蛋白Mps3是复制酵母中心体相当的细胞器纺锤体极体(SPB)所必需的，它参与核组织的多个方面，包括核膜上的端粒拴系和基因沉默，姐妹染色单体凝聚力的建立，以及某些类型的永久性DNA双链断裂的修复。这些不同的太阳蛋白质功能是如何调节的还不清楚。在此，我们在体内外证明了Mps3N-末端是乙酰基转移酶Eco1/Ctf7的底物，并将乙酰化位点定位于Mps3跨膜区附近的三个赖氨酸残基。这些残基的突变表明，乙酰化不是生长、SPB复制或在核膜中分布所必需的。然而，对不可乙酰化的Mps3突变体的分析表明，这种修饰是准确的姐妹染色单体凝聚力和染色体重新募集到核膜所必需的。Eco1对Mps3的乙酰化是已知的控制核组织的为数不多的调控机制之一。
Acetylation of the SUN protein Mps3 by Eco1 regulates nuclear organization, including chromosome cohesion, telomere tethering, and gene silencing, without affecting Mps3 distribution in the nuclear membrane. It is one of the regulatory pathways known to affect chromosome positioning within the nucleus. The Saccharomyces cerevisiae SUN-domain protein Mps3 is required for duplication of the yeast centrosome-equivalent organelle, the spindle pole body (SPB), and it is involved in multiple aspects of nuclear organization, including telomere tethering and gene silencing at the nuclear membrane, establishment of sister chromatid cohesion, and repair of certain types of persistent DNA double-stranded breaks. How these diverse SUN protein functions are regulated is unknown. Here we show that the Mps3 N-terminus is a substrate for the acetyltransferase Eco1/Ctf7 in vitro and in vivo and map the sites of acetylation to three lysine residues adjacent to the Mps3 transmembrane domain. Mutation of these residues shows that acetylation is not essential for growth, SPB duplication, or distribution in the nuclear membrane. However, analysis of nonacetylatable mps3 mutants shows that this modification is required for accurate sister chromatid cohesion and for chromosome recruitment to the nuclear membrane. Acetylation of Mps3 by Eco1 is one of the few regulatory mechanisms known to control nuclear organization.