Scm3 is essential to recruit the histone H3 variant Cse4 to centromeres and to maintain a functional kinetochore
Scm3 is essential to recruit the histone H3 variant Cse4 to centromeres and to maintain a functional kinetochore
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DOI：
10.1016/j.molcel.2007.05.013
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发表时间：
2007-06-22
期刊：
影响因子：
16
通讯作者：
Gerton, Jennifer L.
中科院分区：
文献类型：
--
作者：
Camahort, Raymond;Li, Bing;Gerton, Jennifer L.
动粒是位于着丝粒处的一种复杂的多蛋白结构，对染色体的正确分离至关重要。出芽酵母的Cse4是一种在进化上保守的必需组蛋白H3变体，它通过一种未知机制被招募到着丝粒。我们已经鉴定出Scm3，它是一种内动粒蛋白，能与Cse4一起被免疫纯化。Scm3对细胞活力至关重要，并定位于所有着丝粒。构建一个条件性的SCM3等位基因表明，其缺失会导致中期停滞，伴有纺锤体极复制、纺锤体短小以及DNA分布不均。中期停滞是由有丝分裂纺锤体检查点介导的，该检查点依赖于Mad1和极光激酶B的同源物IpI1。Scm3与Ndc10和Cse4都相互作用，并且对DNA复制后建立着丝粒染色质至关重要。此外，Scm3在整个细胞周期中对维持动粒功能是必需的。我们提出一个模型，其中Ndc10/Scm3与着丝粒DNA结合，这反过来对将Cse4靶向到着丝粒是必不可少的。
The kinetochore is a complex multiprotein structure located at centromeres that is essential for proper chromosome segregation. Budding-yeast Cse4 is an essential evolutionarily conserved histone H3 variant recruited to the centromere by an unknown mechanism. We have identified Scm3, an inner kinetochore protein that immunopurifies with Cse4. Scm3 is essential for viability and localizes to all centromeres. Construction of a conditional SCM3 allele reveals that depletion results in metaphase arrest, with duplicated spindle poles, short spindles, and unequal DNA distribution. The metaphase arrest is mediated by the mitotic spindle checkpoint being dependent on Mad1 and the Aurora kinase B homolog IpI1. Scm3 interacts with both Ndc10 and Cse4 and is essential to establish centromeric chromatin after DNA replication. In addition, Scm3 is required to maintain kinetochore function throughout the cell cycle. We propose a model in which Ndc10/Scm3 binds to centromeric DNA, which is in turn essential for targeting Cse4 to centromeres.