Kireeva Natashe, Lakonishok Margot, Kireev Igor, Hirano Tatsuya, Belmont Andrew S
Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
J Cell Biol. 2004 Sep 13;166(6):775-85. doi: 10.1083/jcb.200406049. Epub 2004 Sep 7.
Current models of mitotic chromosome structure are based largely on the examination of maximally condensed metaphase chromosomes. Here, we test these models by correlating the distribution of two scaffold components with the appearance of prophase chromosome folding intermediates. We confirm an axial distribution of topoisomerase IIalpha and the condensin subunit, structural maintenance of chromosomes 2 (SMC2), in unextracted metaphase chromosomes, with SMC2 localizing to a 150-200-nm-diameter central core. In contrast to predictions of radial loop/scaffold models, this axial distribution does not appear until late prophase, after formation of uniformly condensed middle prophase chromosomes. Instead, SMC2 associates throughout early and middle prophase chromatids, frequently forming foci over the chromosome exterior. Early prophase condensation occurs through folding of large-scale chromatin fibers into condensed masses. These resolve into linear, 200-300-nm-diameter middle prophase chromatids that double in diameter by late prophase. We propose a unified model of chromosome structure in which hierarchical levels of chromatin folding are stabilized late in mitosis by an axial "glue."
当前的有丝分裂染色体结构模型很大程度上基于对高度浓缩的中期染色体的研究。在此，我们通过将两种支架成分的分布与前期染色体折叠中间体的外观相关联来检验这些模型。我们证实，在未提取的中期染色体中，拓扑异构酶IIα和凝聚素亚基染色体结构维持蛋白2（SMC2）呈轴向分布，SMC2定位于直径为150 - 200纳米的中央核心。与径向环/支架模型的预测相反，这种轴向分布直到前期晚期才出现，此时均匀浓缩的中期前期染色体已经形成。相反，SMC2在整个前期早期和中期染色单体中都有结合，经常在染色体外部形成焦点。前期早期的凝聚是通过大规模染色质纤维折叠成浓缩块而发生的。这些浓缩块在中期前期分解为直径为200 - 300纳米的线性染色单体，到前期晚期直径加倍。我们提出了一个统一的染色体结构模型，其中染色质折叠的层次水平在有丝分裂后期通过轴向“胶水”得以稳定。
