Dej Kimberley J, Ahn Caroline, Orr-Weaver Terry L
Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Genetics. 2004 Oct;168(2):895-906. doi: 10.1534/genetics.104.030908.
Chromosomes are dynamic structures that are reorganized during the cell cycle to optimize them for distinct functions. SMC and non-SMC condensin proteins associate into complexes that have been implicated in the process of chromosome condensation. The roles of the individual non-SMC subunits of the complex are poorly understood, and mutations in the CAP-G subunit have not been described in metazoans. Here we elucidate a role for dCAP-G in chromosome condensation and cohesion in Drosophila. We illustrate the requirement of dCAP-G for condensation during prophase and prometaphase; however, we find that alternate mechanisms ensure that replicated chromosomes are condensed prior to metaphase. In contrast, dCAP-G is essential for chromosome condensation in metaphase of single, unreplicated sister chromatids, suggesting that there is an interplay between replicated chromatids and the condensin complex. In the dcap-g mutants, defects in sister-chromatid separation are also observed. Chromatid arms fail to resolve in prophase and are unable to separate at anaphase, whereas sister centromeres show aberrant separation in metaphase and successfully move to spindle poles at anaphase. We also identified a role for dCAP-G during interphase in regulating heterochromatic gene expression.
染色体是动态结构，在细胞周期中会进行重组，以使其功能最优化。SMC和非SMC凝聚蛋白会结合形成复合物，这些复合物与染色体凝聚过程有关。人们对该复合物中各个非SMC亚基的作用了解甚少，并且在后生动物中尚未描述过CAP-G亚基的突变情况。在此，我们阐明了果蝇中dCAP-G在染色体凝聚和黏附中的作用。我们说明了在前期和前中期dCAP-G对凝聚的必要性；然而，我们发现其他机制可确保复制后的染色体在中期之前凝聚。相比之下，dCAP-G对于单个未复制的姐妹染色单体中期的染色体凝聚至关重要，这表明复制后的染色单体与凝聚蛋白复合物之间存在相互作用。在dcap-g突变体中，还观察到姐妹染色单体分离存在缺陷。染色单体臂在前期无法分开，在后期也无法分离，而姐妹着丝粒在中期显示出异常分离，并在后期成功移向纺锤体极。我们还确定了dCAP-G在间期对异染色质基因表达调控中的作用。
