Schmidt Christine K, Brookes Neil, Uhlmann Frank
Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields, London WC2A 3PX, UK.
Genome Biol. 2009;10(5):R52. doi: 10.1186/gb-2009-10-5-r52. Epub 2009 May 19.
Cohesin holds sister chromatids together to enable their accurate segregation in mitosis. How, and where, cohesin binds to chromosomes are still poorly understood, and recent genome-wide surveys have revealed an apparent disparity between its chromosomal association patterns in different organisms.
Here, we present the high-resolution analysis of cohesin localization along fission yeast chromosomes. This reveals that several determinants, thought specific for different organisms, come together to shape the overall distribution. Cohesin is detected at chromosomal loading sites, characterized by the cohesin loader Mis4/Ssl3, in regions of strong transcriptional activity. Cohesin also responds to transcription by downstream translocation and accumulation at convergent transcriptional terminators surrounding the loading sites. As cells enter mitosis, a fraction of cohesin leaves chromosomes in a cleavage-independent reaction, while a substantial pool of cohesin dissociates when it is cleaved at anaphase onset. We furthermore observe that centromeric cohesin spreads out onto chromosome arms during mitosis, dependent on Aurora B kinase activity, emphasizing the plasticity of cohesin behavior.
Our findings suggest that features that were thought to differentiate cohesin between organisms collectively define the overall behavior of fission yeast cohesin. Apparent differences between organisms might reflect an emphasis on different aspects, rather than different principles, of cohesin action.
黏连蛋白将姐妹染色单体结合在一起,使其在有丝分裂中能够准确分离。黏连蛋白如何以及在何处与染色体结合仍知之甚少,最近的全基因组调查揭示了其在不同生物体中的染色体关联模式存在明显差异。
在此,我们展示了对裂殖酵母染色体上黏连蛋白定位的高分辨率分析。这表明,一些被认为是不同生物体特有的决定因素共同塑造了整体分布。在强转录活性区域的染色体装载位点(其特征为黏连蛋白装载因子Mis4/Ssl3)检测到黏连蛋白。黏连蛋白还通过下游易位并在装载位点周围的汇聚转录终止子处积累来响应转录。当细胞进入有丝分裂时,一部分黏连蛋白以不依赖于切割的反应离开染色体,而大量的黏连蛋白在后期开始时被切割时解离。我们还观察到,着丝粒黏连蛋白在有丝分裂期间扩散到染色体臂上,这依赖于极光B激酶活性,强调了黏连蛋白行为的可塑性。
我们的研究结果表明,那些被认为区分不同生物体中黏连蛋白的特征共同定义了裂殖酵母黏连蛋白的整体行为。生物体之间的明显差异可能反映了对黏连蛋白作用的不同方面而非不同原理的强调。