A novel role for the CBF3 kinetochore-scaffold complex in regulating septin dynamics and cytokinesis.

A novel role for the CBF3 kinetochore-scaffold complex in regulating septin dynamics and cytokinesis.
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DOI:
10.1083/jcb.200507017
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发表时间:
2005-12-05
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Kaplan KB
Kaplan KB
中科院分区:
其他
文献类型:
--
作者:
Gillis AN;Thomas S;Hansen SD;Kaplan KB

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在芽殖酵母中,着丝粒结合因子3(CBF 3)是着丝粒DNA上形成着丝粒并允许适当染色体分离所必需的着丝粒支架复合物。我们先前已经表明SKP 1和SGT 1平衡CBF 3复合物的组装和周转,我们认为这是一个独立于其在染色体分离中的作用的循环(Rodrigo-Brenni,M.C.,S.托马斯、D.C.布克和K. B.卡普兰2004.摩尔生物细胞15:3366-3378)。我们提供的证据表明,这一周期有助于第二个,不依赖于CBF 3的kinetochorse功能。在这项研究中,我们表明,抑制CBF 3的组装会导致细胞分裂素紊乱和细胞极性缺陷,从而导致胞质分裂失败。具体来说,我们发现,septin环分离和拆卸延迟后期,这表明CBF 3调节septin动力学。只有影响CBF 3循环的突变,而不是外动粒亚基的突变,才会导致septins的缺陷。这些结果证明了CBF 3在调节胞质分裂中的新作用,这种作用让人想起乘客蛋白。与这种可能性相一致,我们发现CBF 3与Bir 1 p相互作用,Bir 1 p是乘客蛋白Survivin的同源物。Bir 1 p的突变体同样影响septin组织,这使我们提出CBF 3和Bir 1 p作为乘客蛋白来协调染色体分离与胞质分裂。
In budding yeast, the kinetochore scaffold complex centromere binding factor 3 (CBF3) is required to form kinetochores on centromere DNA and to allow proper chromosome segregation. We have previously shown that SKP1 and SGT1 balance the assembly and turnover of CBF3 complexes, a cycle that we suggest is independent of its role in chromosome segregation (Rodrigo-Brenni, M.C., S. Thomas, D.C. Bouck, and K.B. Kaplan. 2004. Mol. Biol. Cell. 15:3366–3378). We provide evidence that this cycle contributes to a second, kinetochore-independent function of CBF3. In this study, we show that inhibiting the assembly of CBF3 causes disorganized septins and defects in cell polarity that give rise to cytokinesis failures. Specifically, we show that septin ring separation and disassembly is delayed in anaphase, suggesting that CBF3 regulates septin dynamics. Only mutations that affect the CBF3 cycle, and not mutants in outer kinetochore subunits, cause defects in septins. These results demonstrate a novel role for CBF3 in regulating cytokinesis, a role that is reminiscent of passenger proteins. Consistent with this possibility, we find that CBF3 interacts with Bir1p, the homologue of the passenger protein Survivin. Mutants in Bir1p similarly affect septin organization, leading us to propose that CBF3 and Bir1p act as passenger proteins to coordinate chromosome segregation with cytokinesis.
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