An SMC-domain protein in fission yeast links telomeres to the meiotic centrosome
An SMC-domain protein in fission yeast links telomeres to the meiotic centrosome
复制标题
DOI：
10.1016/j.molcel.2004.10.027
复制
发表时间：
2004-11-19
期刊：
影响因子：
16
通讯作者：
Aebersold, R
中科院分区：
文献类型：
--
作者：
Flory, MR;Carson, AR;Aebersold, R
裂殖酵母中中心周蛋白同源物 Pcp1p 的过度表达可诱导与人类癌症中发生的异常中心体结构相似的异常中心体结构。通过定量质谱和同位素编码亲和标签对含有 Pcp1p 的异常结构进行分析，鉴定出一种卷曲螺旋、染色体结构维持 (SMC) 结构域蛋白。这种蛋白质被称为 Ccq1p（卷曲螺旋蛋白定量富集），与 Taz1p 一起定位于正常营养细胞的端粒。荧光共振能量转移 (FRET) 测量表明，在交配信息素刺激的含有中心体簇集端粒的细胞中，Ccq1p 还与中心体 Pcp1p 相互作用。我们提供的证据表明，Ccq1p-Pcp1p 相互作用虽然对于减数分裂至关重要，但在营养生长期间被迫发生时是有害的。缺乏一个 ccq1 等位基因的细胞表现出功能丧失的表型，包括异常长的细胞长度、染色体分离失败、端粒缩短和减数分裂前期端粒聚集缺陷。我们的数据表明了减数分裂染色体花束形成的潜在机制，并提出了多余中心体毒性的招募模型。
Abnormal centrosomal structures similar to those occurring in human cancers are induced in fission yeast by overexpression of the pericentrin homolog Pcp1p. Analysis of abnormal Pcp1p-containing structures with quantitative mass spectrometry and isotope-coded affinity tags identified a coiled-coil, structural maintenance of chromosomes (SMC) domain protein. This protein, termed Ccq1p (coiled-coil protein quantitatively enriched), localizes with Taz1p to telomeres in normal vegetative cells. Fluorescence resonance energy transfer (FRET) measurements indicate that Ccq1p also interacts with centrosomal Pcp1p in mating pheromone-stimulated cells containing centrosomally clustered telomeres. We provide evidence that the Ccq1p-Pcp1p interaction, while essential for meiosis, is deleterious when forced to occur during vegetative growth. Cells lacking one ccq1 allele exhibit a loss-of-function phenotype including abnormally long cell length, chromosome segregation failure, telomeric shortening, and defective telomeric clustering during meiotic prophase. Our data indicate a mechanism underlying meiotic chromosomal bouquet formation and suggest a recruitment model for supernumerary centrosome toxicity.