Choy John S, Mishra Prashant K, Au Wei-Chun, Basrai Munira A
Genetics Branch Center for Cancer research, National Cancer Institute, National Institutes of Health, 41 Medlars Drive, Bethesda, MD 20892, USA.
Biochim Biophys Acta. 2012 Jul;1819(7):776-83. doi: 10.1016/j.bbagrm.2012.02.008. Epub 2012 Feb 16.
At the core of chromosome segregation is the centromere, which nucleates the assembly of a macromolecular kinetochore (centromere DNA and associated proteins) complex responsible for mediating spindle attachment. Recent advances in centromere research have led to identification of many kinetochore components, such as the centromeric-specific histone H3 variant, CenH3, and its interacting partner, Scm3. Both are essential for chromosome segregation and are evolutionarily conserved from yeast to humans. CenH3 is proposed to be the epigenetic mark that specifies centromeric identity. Molecular mechanisms that regulate the assembly of kinetochores at specific chromosomal sites to mediate chromosome segregation are not fully understood. In this review, we summarize the current literature and discuss results from our laboratory, which show that restricting the localization of budding yeast CenH3, Cse4, to centromeres and balanced stoichiometry between Scm3 and Cse4, contribute to faithful chromosome transmission. We highlight our findings that, similar to other eukaryotic centromeres, budding yeast centromeric histone H4 is hypoacetylated, and we discuss how altered histone acetylation affects chromosome segregation. This article is part of a Special Issue entitled: Chromatin in time and space.
染色体分离的核心是着丝粒，它能促使一个负责介导纺锤体附着的大分子动粒（着丝粒DNA及相关蛋白质）复合体组装。着丝粒研究的最新进展已使得许多动粒组分得以鉴定，比如着丝粒特异性组蛋白H3变体CenH3及其相互作用伴侣Scm3。二者对于染色体分离均至关重要，且从酵母到人类在进化上是保守的。CenH3被认为是指定着丝粒身份的表观遗传标记。调控动粒在特定染色体位点组装以介导染色体分离的分子机制尚未完全明了。在本综述中，我们总结了当前文献并讨论了我们实验室的结果，这些结果表明，将芽殖酵母CenH3（Cse4）的定位限制在着丝粒以及Scm3与Cse4之间平衡的化学计量比有助于染色体的准确传递。我们强调我们的发现，即与其他真核生物着丝粒类似，芽殖酵母着丝粒组蛋白H4是低乙酰化的，并且我们讨论了组蛋白乙酰化改变如何影响染色体分离。本文是名为“时空染色质”的特刊的一部分。
