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Heterochromatin Links To Centromeric Protection By Recruiting Shugoshin

机译:异染色质通过招募Shugoshin链接到着丝粒保护

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摘要

The centromere of a chromosome is composed mainly of two domains, a kinetochore assembling core centromere and peri-centromeric heterochromatin regions. The crucial role of centromeric heterochromatin is still unknown, because even in simpler unicellular organisms such as the fission yeast Schizosaccharomyces pombe, the heterochromatin protein Swi6 (HP1 homologue) has several functions at centromeres, including silencing gene expression and recombination, enriching cohesin, promoting kinetochore assembly, and, ultimately, preventing erroneous microtubule attachment to the kinetochores. Here we show that the requirement of heterochromatin for mitotic chromosome segregation is largely replaced by forcibly enriching cohesin at centromeres in fission yeast. However, this enrichment of cohesin is not sufficient to replace the meiotic requirement for heterochromatin. We find that the heterochromatin protein Swi6 associates directly with meiosis-specific shugoshin Sgol, a protector of cohesin at centromeres. A point mutation of Sgol (V242E), which abolishes the interaction with Swi6, impairs the centromeric localization and function of Sgol. The forced centromeric localization of Sgol restores proper meiotic chromosome segregation in swi6 △ cells. We also show that the direct link between HP1 and shugoshin is conserved in human cells. Taken together, our findings suggest that the recruitment of shugoshin is the important primary role for centromeric heterochromatin in ensuring eukaryotic chromosome segregation.
机译:染色体的着丝粒主要由两个域组成,一个集线粒体组装核心着丝粒和近着丝粒异染色质区域。着丝粒异染色质的关键作用仍是未知的,因为即使在诸如裂殖酵母裂殖酵母等简单的单细胞生物中,异染色质蛋白Swi6(HP1同源物)在着丝粒上也具有多种功能,包括沉默基因表达和重组,丰富粘蛋白,促进动粒体。组装,并最终防止错误的微管附着在动植物上。在这里,我们显示异染色质对有丝分裂染色体分离的要求已在裂变酵母的着丝粒上被强制富集的粘着蛋白大大取代。但是,这种凝聚素的富集不足以替代异染色质的减数分裂需求。我们发现异染色质蛋白Swi6直接与减数分裂特异的守护甜心素Sgol,着丝粒的cohesin的保护者。 Sgol(V242E)的点突变消除了与Swi6的相互作用,削弱了Sgol着丝粒的定位和功能。 Sgol的强制着丝粒定位可恢复swi6△细胞中适当的减数分裂染色体分离。我们还表明,HP1和shugoshin之间的直接联系在人类细胞中是保守的。综上所述,我们的发现表明,将人参精蛋白的募集是着丝粒异染色质在确保真核染色体分离中的重要主要作用。

著录项

  • 来源
    《Nature》 |2008年第7210期|p.251-255|共5页
  • 作者单位

    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
  • 关键词

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