PLoS Biology:可视化的细胞分裂

2011-06-15 15:07 · Abel

摘要:基因控制着一切,从眼睛的颜色、对疾病的敏感性到遗传。基因经过复制,一代又一代地传递下去,这样的过依赖于着丝粒。 着丝粒位于每一个染色体上的“小掐腰”处,着丝粒控制着细胞分裂时姐妹染色单体的分离,以确保每个子细胞能够获得每条染色体的完整信息。 人们早就知道,着丝粒并不是完全由

摘要:基因控制着一切,包括眼睛的颜色、对疾病的易感性等,这样的过程依赖于着丝粒。基因经过复制,一代又一代地传递下去。着丝粒位于每一个染色体上的“小掐腰”处,着丝粒控制着细胞分裂时姐妹染色单体的分离,以确保每个子细胞能够获得每条染色体的完整信息。 人们早就知道,着丝粒并不是完全由DNA来形成,相反,着丝粒蛋白(CENPs)可以帮助着丝粒在染色体上的装配。 蛋白质是如何一代又一代地进行精确的复制,并且保持稳定的结构与性能?这一直是个谜。 由Kevin Sullivan教授领导的爱尔兰Galway染色体生物学中心的研究人员,将细胞分裂中的蛋白质可视化了,这样可以来分析这些部分是如何随着人类细胞的生长和分裂来组装成着丝粒的。这项新的研究在线发表于6月14日的PLoS Biology 。

Galway研究小组利用了一种荧光标记方法,在显微镜下观察活细胞染色体上CENPs的复制,他们还看到细胞分裂时去除CENPs后,染色体是如何运动的。

这项新研究提供了重要的实验和观念上的工具,将有助于阐明在正常的发育和疾病中,表观遗传学是怎样起作用的。

 

生物探索推荐英文原文:

New light shed on cell division

Genes control everything from eye color to disease susceptibility, and inheritance - the passing of the genes from generation to generation after they have been duplicated - depends on centromeres. Located in the little pinched waist of each chromosome, centromeres control the movements that separate sister chromosomes when cells divide ensuring that each daughter cell inherits a complete copy of each chromosome. It has long been known that centromeres are not formed solely from DNA; rather, centromere proteins (CENPs) facilitate the assembly of a centromere on each chromosome. Understanding how a protein structure can be copied with enough precision to be stable, generation after generation, has been a mystery. Researchers at the Centre for Chromosome Biology in Galway, Ireland, led by Professor Kevin Sullivan, have visualized these proteins in living cells to analyse how the parts of centromeres assemble themselves as human cells grow and divide. Their new study will be published on 14 June in the online, open access journal PloS Biology.

The Galway group used fluorescent labeling methods to observe the duplication of CENPs on the chromosomes in live cells under the microscope. They also watched how chromosome movement goes awry during cell division when key CENPs were removed from the cell. By comparing how different CENPs are made and then packaged on chromosomes, lead researcher Dr Lisa Prendergast discovered an essential division of labor among the CENPs. A key protein known as CENP-A seems to be specialized for carrying the genetic information of the centromere. Molecular cousins known as CENPs –T and –W assemble beside CENP-A along the chromosome fiber only after DNA has been replicated. They then go on to do the 'heavy lifting' involved in motoring chromosomes through cell division by producing a structure known as the kinetochore.

It is known that chromosomes inherit more information than is carried in the genes - the field of epigenetics is the study of how a single set of genes can be used to make over 200 different types of cell that make up the body. The centromere is a very special epigenetic element, in which identity itself is carried outside the DNA. This new study provides important experimental and conceptual tools that will help illuminate broader questions about how epigenetics works in normal development and in disease. But because the centromere works at the heart of cell division, it has special relevance in the fight against cancer. Many chemotherapy drugs act by stopping cell division, but their targets also have other roles in the cell, leading to toxic effects in the nervous system and in the rapidly growing cells of hair and skin, for example. "By understanding the inner workings of this molecular machine at a deeper level, we can now think of how to build drugs that target cancer cell division with much greater precision," says Professor Sullivan. "It's important to see how basic research, aimed solely at understanding how life works, can contribute new ideas that support progress in medicine and therapeutics."

By clearly separating genetic inheritance from kinetochore function into different domains on the chromosome fiber, research into cell division and how to stop it in cancer cells can now take place at an accelerated pace.

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