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New clues to understand how CENP-A maintains centromere identity

机译：了解CENP-A如何保持着丝粒身份的新线索

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The centromere is a specialized chromosomal region that directs the formation of the kinetochore, a huge protein assembly that acts as the attachment site for spindle microtubules and carries out chromosome movement during cell division. Centromere loss or the presence of extra centromeres adversely affect chromosome segregation and may result in aneuploidy, a condition found in many human tumors and a major cause of miscarriages and birth defects. Consequently, understanding the basis of centromere determination and propagation is of great relevance to both fundamental and clinical research. In recent years, it has become clear that centromeres are defined by the presence of a histone H3 variant known as Centromere Protein A, CENP-A, or CenH3. Much effort has been devoted to understanding the mechanisms that drive the assembly of CENP-A containing nucleosomes exclusively onto centromeric DNA, as well as the peculiar structure of these nucleosomes. We have recently developed an immunofluorescence-based assay that measures CENP-A incorporation in the centromeres of chromosomes assembled in Xenopus egg extracts. The spatial and temporal specificity of CENP-A deposition observed in human cells can be recapitulated in this in vitro system, making it suitable to dissect the precise role of the different factors that contribute to this pathway. Here, we discuss our results together with other recent advances in our understanding of the mechanisms that mediate centromere inheritance.
机译：着丝粒是一个专门的染色体区域，指导着动粒的形成，这是一个巨大的蛋白质装配体，它充当纺锤体微管的附着位点，并在细胞分裂过程中进行染色体运动。着丝粒的丢失或着丝粒的存在会对染色体的分离产生不利影响，并可能导致非整倍性，这是在许多人类肿瘤中发现的状况，也是流产和出生缺陷的主要原因。因此，了解着丝粒测定和繁殖的基础与基础研究和临床研究都息息相关。近年来，很明显，着丝粒是通过存在称为着丝粒蛋白A，CENP-A或CenH3的组蛋白H3变体来定义的。已经进行了很多努力来理解驱动仅将含CENP-A的核小体组装到着丝粒DNA上的机制，以及这些核小体的特殊结构。我们最近开发了一种基于免疫荧光的检测方法，用于测量非洲爪蟾卵提取物中组装的染色体着丝粒中CENP-A的掺入。可以在此体外系统中概括人类细胞中观察到的CENP-A沉积的时空特异性，使其适合剖析促成该途径的不同因素的确切作用。在这里，我们将讨论我们的结果，以及我们对介导着丝粒遗传的机制的其他最新进展。

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