Investigating the Interplay between Sister Chromatid Cohesion and Homolog Pairing in Drosophila Nuclei.
Investigating the Interplay between Sister Chromatid Cohesion and Homolog Pairing in Drosophila Nuclei.
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DOI：
10.1371/journal.pgen.1006169
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发表时间：
2016-08
期刊：
影响因子：
4.5
通讯作者：
Wu CT
中科院分区：
文献类型：
--
作者：
Senaratne TN;Joyce EF;Nguyen SC;Wu CT
在DNA复制之后，姐妹染色单体必须在细胞周期的剩余时间内保持连接，以确保在随后的细胞分裂中准确分离。这一重要功能涉及一种进化上保守的蛋白质复合物，即黏结蛋白；在有丝分裂中，任何内聚蛋白的丢失都会导致姊妹染色单体过早分离。本研究利用荧光原位杂交技术（FISH）检测果蝇细胞间期姐妹染色单体的排列，研究了有丝分裂前凝聚蛋白在姐妹染色单体内聚中的作用。令人惊讶的是，我们发现在G2中姐妹染色单体的内聚可以在很少或没有内聚的情况下保持。这种维持内聚的能力在果蝇中广泛存在，不像在其他系统中，姐妹染色单体分离对内聚蛋白的依赖性降低仅在特定染色体区域被观察到，例如出芽酵母的rDNA位点。此外，我们表明凝聚蛋白II在间期拮抗姐妹染色单体的排列，支持一个模型，其中凝聚蛋白和凝聚蛋白II在姐妹染色单体的排列中相互对立的功能。最后，由于母系和父系同源染色体在果蝇体细胞中是配对的，并且由于凝缩蛋白II已被证明可以拮抗这种配对，我们认为凝缩蛋白II调节的同源染色体排列机制可能也有助于姐妹染色单体的内聚。随着细胞的生长，它们复制自己的DNA，产生每条染色体的两个副本，称为姐妹染色单体，一旦细胞分裂，它们就会彼此分离。为了确保姐妹染色单体最终进入不同的子细胞，它们通过一种称为内聚的连接从DNA复制一直保持在一起，直到有丝分裂。一种被称为黏结蛋白的蛋白质复合物在这个过程中是必不可少的。我们在果蝇细胞中的研究表明，除了内聚蛋白外，其他因素也有助于姐妹染色单体间期的内聚。此外，我们观察到姐妹染色单体的排列受到凝缩蛋白II的调节，凝缩蛋白II是一种蛋白质复合物，参与染色体分裂前的压实以及染色体间关联的调节。这些发现强调，除了它们重要的个体功能外，内聚蛋白和凝缩蛋白II可能在细胞周期过程中相互作用来组织染色体。最后，基于先前对浓缩蛋白II参与果蝇体细胞同源配对调控的观察，我们的工作表明同源配对的潜在机制也可能有助于姐妹染色单体内聚。
Following DNA replication, sister chromatids must stay connected for the remainder of the cell cycle in order to ensure accurate segregation in the subsequent cell division. This important function involves an evolutionarily conserved protein complex known as cohesin; any loss of cohesin causes premature sister chromatid separation in mitosis. Here, we examined the role of cohesin in sister chromatid cohesion prior to mitosis, using fluorescence in situ hybridization (FISH) to assay the alignment of sister chromatids in interphase Drosophila cells. Surprisingly, we found that sister chromatid cohesion can be maintained in G2 with little to no cohesin. This capacity to maintain cohesion is widespread in Drosophila, unlike in other systems where a reduced dependence on cohesin for sister chromatid segregation has been observed only at specific chromosomal regions, such as the rDNA locus in budding yeast. Additionally, we show that condensin II antagonizes the alignment of sister chromatids in interphase, supporting a model wherein cohesin and condensin II oppose each other’s functions in the alignment of sister chromatids. Finally, because the maternal and paternal homologs are paired in the somatic cells of Drosophila, and because condensin II has been shown to antagonize this pairing, we consider the possibility that condensin II-regulated mechanisms for aligning homologous chromosomes may also contribute to sister chromatid cohesion. As cells grow, they replicate their DNA to give rise to two copies of each chromosome, known as sister chromatids, which separate from each other once the cell divides. To ensure that sister chromatids end up in different daughter cells, they are kept together from DNA replication until mitosis via a connection known as cohesion. A protein complex known as cohesin is essential for this process. Our work in Drosophila cells suggests that factors other than cohesin also contribute to sister chromatid cohesion in interphase. Additionally, we observed that the alignment of sister chromatids is regulated by condensin II, a protein complex involved in the compaction of chromosomes prior to division as well as the regulation of inter-chromosomal associations. These findings highlight that, in addition to their important individual functions, cohesin and condensin II proteins may interact to organize chromosomes over the course of the cell cycle. Finally, building on prior observations that condensin II is involved in the regulation of somatic homolog pairing in Drosophila, our work suggests that the mechanisms underlying homolog pairing may also contribute to sister chromatid cohesion.