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端粒锚定在核膜周边需要芽殖酵母中含Sad1-UNC-84结构域的蛋白Mps3。

Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3.

作者信息

Bupp Jennifer M, Martin Adriana E, Stensrud Elizabeth S, Jaspersen Sue L

机构信息

Stowers Institute for Medical Research, Kansas City, MO 64110, USA.

出版信息

J Cell Biol. 2007 Dec 3;179(5):845-54. doi: 10.1083/jcb.200706040. Epub 2007 Nov 26.

DOI:10.1083/jcb.200706040
PMID:18039933
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2099192/
Abstract

Positioning of telomeres at the nuclear periphery can have dramatic effects on gene expression by establishment of heritable, transcriptionally repressive subdomains. However, little is known about the integral membrane proteins that mediate telomere tethering at the nuclear envelope. Here, we find a previously unrecognized function for the Saccharomyces cerevisiae Sad1-UNC-84 domain protein Mps3 in regulating telomere positioning in mitotic cells. Our data demonstrate that the nucleoplasmic N-terminal acidic domain of Mps3 is not essential for viability. However, this acidic domain is necessary and sufficient for telomere tethering during S phase and the silencing of reporter constructs integrated at telomeres. We show that this is caused by the role of the Mps3 acidic domain in binding and localization of the silent information regulator protein Sir4 to the nuclear periphery. Thus, Mps3 functions as an integral membrane anchor for telomeres and is a novel nuclear receptor for the Sir4 pathway of telomere tethering and gene inactivation.

摘要

端粒定位于核周边可通过建立可遗传的转录抑制亚结构域对基因表达产生显著影响。然而,对于介导端粒在核膜上锚定的整合膜蛋白却知之甚少。在此,我们发现酿酒酵母Sad1-UNC-84结构域蛋白Mps3在调节有丝分裂细胞中端粒定位方面具有先前未被认识的功能。我们的数据表明,Mps3的核质N端酸性结构域对细胞活力并非必需。然而,该酸性结构域对于S期的端粒锚定以及整合在端粒处的报告基因构建体的沉默是必要且充分的。我们表明,这是由Mps3酸性结构域在将沉默信息调节蛋白Sir4结合并定位到核周边中的作用所导致的。因此,Mps3作为端粒的整合膜锚定物,是端粒锚定和基因失活的Sir4途径的新型核受体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82a4/2099192/16aa0507cf9a/jcb1790845f08.jpg
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