C-elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis
C-elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis
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DOI：
10.1101/gad.968302
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发表时间：
2002-03-15
影响因子：
10.5
通讯作者：
Meyer, BJ
中科院分区：
文献类型：
--
作者：
Hagstrom, KA;Holmes, VF;Meyer, BJ
秀丽隐杆线虫的染色体分离和X染色体基因调控共享MIX-1，一种有丝分裂蛋白，在剂量补偿期间也抑制X连锁基因。MIX-1通过与不同蛋白质伴侣的相互作用实现其双重作用。为了抑制基因表达，MIX-1在X染色体复合体中起作用，该复合体类似于有丝分裂凝聚素复合体，但缺乏染色体分离功能。在这里，我们表明，MIX-1与有丝分裂凝聚素亚基，SMC-4，实现染色体分离。SMC-4/MIX-1复合物在体外积极超螺旋DNA，并需要有丝分裂染色体的结构和分离在体内。因此，C.线虫有两个凝聚素复合物，一个保守用于有丝分裂，另一个专门用于基因调控。SMC-4和MIX-1与着丝粒蛋白共定位在浓缩的有丝分裂染色体上，并且是着丝粒朝向纺锤体极的限制性取向所必需的。这种细胞周期依赖性定位需要AIR-2/AuroraB激酶。SMC-4/MIX-1的缺失导致异常的有丝分裂染色体结构和分离，但在中期没有显著的解凝聚。此外，SMC-4/MIX-1耗竭破坏减数分裂II期间的姐妹染色单体分离，但不破坏减数分裂1期间的同源染色体分离，尽管这两个过程都需要染色体凝聚。这些结果表明，凝聚素是不是简单地需要压实，但在染色体结构中起着更复杂的作用，是必不可少的有丝分裂和减数分裂姐妹染色单体分离。
Chromosome segregation and X-chromosome gene regulation in Caenorhabditis elegans share the component MIX-1, a mitotic protein that also represses X-linked genes during dosage compensation. MIX-1 achieves its dual roles through interactions with different protein partners. To repress gene expression, MIX-1 acts in an X-chromosome complex that resembles the mitotic condensin complex yet lacks chromosome segregation function. Here we show that MIX-1 interacts with a mitotic condensin subunit, SMC-4, to achieve chromosome segregation. The SMC-4/MIX-1 complex positively supercoils DNA in vitro and is required for mitotic chromosome structure and segregation in vivo. Thus, C. elegans has two condensin complexes, one conserved for mitosis and another specialized for gene regulation. SMC-4 and MIX-1 colocalize with centromere proteins on condensed mitotic chromosomes and are required for the restricted orientation of centromeres toward spindle poles. This cell cycle-dependent localization requires AIR-2/AuroraB kinase. Depletion of SMC-4/MIX-1 causes aberrant mitotic chromosome structure and segregation, but not dramatic decondensation at metaphase. Moreover, SMC-4/MIX-1 depletion disrupts sister chromatid segregation during meiosis II but not homologous chromosome segregation during meiosis 1, although both processes require chromosome condensation. These results imply that condensin is not simply required for compaction, but plays a more complex role in chromosome architecture that is essential for mitotic and meiotic sister chromatid segregation.