Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis.

Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis.
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DOI:
10.1371/journal.pone.0007701
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发表时间:
2009-11-02
期刊:
影响因子:
3.7
通讯作者:
Sun QY
Sun QY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li M;Li S;Yuan J;Wang ZB;Sun SC;Schatten H;Sun QY

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在有丝分裂中,纺锤体组装检查点 (SAC) 可以防止后期开始,直到所有染色体都附着到纺锤体微管并在赤道中期板正确对齐。有丝分裂中的主要检查点蛋白包括有丝分裂停滞缺陷 (Mad)1-3、不受苯并咪唑 (Bub)1、Bub3 和单极纺锤体 1 (Mps1) 抑制的出芽。在减数分裂过程中,为了形成单倍体配子,连续发生两轮染色体分离,仅进行一轮DNA复制。为了在减数分裂 I 期间将同源染色体拉向相反的纺锤体极,同源染色体的两个姐妹动粒必须面向同一极,这与有丝分裂和减数分裂 II 非常不同。作为检查点蛋白的核心成员,Bub3在哺乳动物卵母细胞减数分裂中的个体作用尚不清楚。在本研究中,我们使用过表达和 RNA 干扰 (RNAi) 方法分析了 Bub3 在小鼠卵母细胞减数分裂中的作用。我们的数据表明,过表达的 Bub3 通过分别阻止减数分裂 I 和 II 中的同源染色体和姐妹染色单体分离来抑制减数分裂中期 - 后期转变。在Bub3敲低的卵母细胞中观察到染色体错位、异常极体和双极体,导致非整倍体。此外,通过冷处理结合Bub3过表达,我们发现过表达的Bub3影响中期-后期转变期间微管和动粒的附着。我们认为,作为 SAC 的成员,Bub3 是减数分裂 I 和 II 的调节所必需的,并且可能参与哺乳动物卵母细胞中着丝粒-微管的附着。
In mitosis, the spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes have been attached to the spindle microtubules and aligned correctly at the equatorial metaphase plate. The major checkpoint proteins in mitosis consist of mitotic arrest-deficient (Mad)1–3, budding uninhibited by benzimidazole (Bub)1, Bub3, and monopolar spindle 1(Mps1). During meiosis, for the formation of a haploid gamete, two consecutive rounds of chromosome segregation occur with only one round of DNA replication. To pull homologous chromosomes to opposite spindle poles during meiosis I, both sister kinetochores of a homologue must face toward the same pole which is very different from mitosis and meiosis II. As a core member of checkpoint proteins, the individual role of Bub3 in mammalian oocyte meiosis is unclear. In this study, using overexpression and RNA interference (RNAi) approaches, we analyzed the role of Bub3 in mouse oocyte meiosis. Our data showed that overexpressed Bub3 inhibited meiotic metaphase-anaphase transition by preventing homologous chromosome and sister chromatid segregations in meiosis I and II, respectively. Misaligned chromosomes, abnormal polar body and double polar bodies were observed in Bub3 knock-down oocytes, causing aneuploidy. Furthermore, through cold treatment combined with Bub3 overexpression, we found that overexpressed Bub3 affected the attachments of microtubules and kinetochores during metaphase-anaphase transition. We propose that as a member of SAC, Bub3 is required for regulation of both meiosis I and II, and is potentially involved in kinetochore-microtubule attachment in mammalian oocytes.
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发表时间: 1998-03-19
期刊: NATURE
影响因子: 64.8
作者:
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