A role for the CAL1-partner Modulo in centromere integrity and accurate chromosome segregation in Drosophila.

A role for the CAL1-partner Modulo in centromere integrity and accurate chromosome segregation in Drosophila.
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DOI:
10.1371/journal.pone.0045094
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Mellone BG
Mellone BG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen CC;Greene E;Bowers SR;Mellone BG

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核仁和着丝粒之间的关系,尽管有文献记载,但仍然是着丝粒组装和维护中最难以捉摸的方面之一。在这里,我们确定了核仁蛋白MODULO,在与CAL1的复合体中,CAL1是着丝粒特异性组蛋白H3变体CID在果蝇中着丝粒沉积所必需的因子。值得注意的是,CAL1定位于着丝粒和核仁。RNAi耗尽了modulo,导致了新合成的CAL1在着丝粒上的缺陷招募。此外,MODULO的缺失对着丝粒的CID水平产生负面影响,并导致染色体错误分离。有趣的是,对有丝分裂过程中模数定位的检测表明,它定位于染色体外围,而不是着丝粒。综上所述,这些数据表明,通过指导CAL1的定位来调节着丝粒的组装,而不是对着丝粒的直接调节作用,而是模数的核仁功能。我们认为,果蝇的核仁和着丝粒组装之间存在功能联系,这种联系受Modulo的调节。
The relationship between the nucleolus and the centromere, although documented, remains one of the most elusive aspects of centromere assembly and maintenance. Here we identify the nucleolar protein, Modulo, in complex with CAL1, a factor essential for the centromeric deposition of the centromere-specific histone H3 variant, CID, in Drosophila. Notably, CAL1 localizes to both centromeres and the nucleolus. Depletion of Modulo, by RNAi, results in defective recruitment of newly-synthesized CAL1 at the centromere. Furthermore, depletion of Modulo negatively affects levels of CID at the centromere and results in chromosome missegregation. Interestingly, examination of Modulo localization during mitosis reveals it localizes to the chromosome periphery but not the centromere. Combined, the data suggest that rather than a direct regulatory role at the centromere, it is the nucleolar function of modulo which is regulating the assembly of the centromere by directing the localization of CAL1. We propose that a functional link between the nucleolus and centromere assembly exists in Drosophila, which is regulated by Modulo.
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