Slk19 clusters kinetochores and facilitates chromosome bipolar attachment.
Slk19 clusters kinetochores and facilitates chromosome bipolar attachment.
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DOI：
10.1091/mbc.e12-07-0552
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发表时间：
2013-03
影响因子：
3.3
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Richmond D;Rizkallah R;Liang F;Hurt MM;Wang Y
酵母着丝粒蛋白Slk19是着丝粒聚集所必需的，nocodazole暴露于Slk19突变细胞会导致着丝粒捕获受损，并在nocodazole洗除后延迟染色体双极性附着。在所有真核细胞中，DNA被包装成多条染色体，这些染色体通过一种叫做着丝点的大蛋白质复合物与微管相连。以往的研究表明，在细胞周期的大部分时间内，着丝点聚集在一起，但其聚集的机制和生物学意义尚不清楚。Slk19作为出芽酵母的着丝点蛋白，在后期纺锤体稳定性中的作用已经得到了很好的研究，但其在染色体分离中的功能尚不清楚。本研究表明，当酵母细胞用微管解聚剂nocodazole处理时，Slk19是着丝点聚集所必需的。我们进一步发现slk19Δ突变细胞在nocodazole破坏着丝点-微管相互作用后表现出延迟的着丝点捕获和染色体双极性附着，这可能归因于有缺陷的着丝点聚集。此外，我们发现Slk19与自身相互作用，这表明Slk19的二聚化可能介导着丝点之间的相互作用。因此，Slk19可能作为着丝点胶，聚集着丝点以促进有效和忠实的染色体分离。
Yeast kinetochore protein Slk19 is required for kinetochore clustering, and nocodazole exposure to slk19 mutant cells causes impaired kinetochore capture and delayed chromosome bipolar attachment after nocodazole washout. In all eukaryotic cells, DNA is packaged into multiple chromosomes that are linked to microtubules through a large protein complex called a kinetochore. Previous data show that the kinetochores are clustered together during most of the cell cycle, but the mechanism and the biological significance of kinetochore clustering are unknown. As a kinetochore protein in budding yeast, the role of Slk19 in the stability of the anaphase spindle has been well studied, but its function in chromosome segregation has remained elusive. Here we show that Slk19 is required for kinetochore clustering when yeast cells are treated with the microtubule-depolymerizing agent nocodazole. We further find that slk19Δ mutant cells exhibit delayed kinetochore capture and chromosome bipolar attachment after the disruption of the kinetochore–microtubule interaction by nocodazole, which is likely attributed to defective kinetochore clustering. In addition, we show that Slk19 interacts with itself, suggesting that the dimerization of Slk19 may mediate the interaction between kinetochores for clustering. Therefore Slk19 likely acts as kinetochore glue that clusters kinetochores to facilitate efficient and faithful chromosome segregation.