In vivo requirements for rDNA chromosome condensation reveal two cell-cycle-regulated pathways for mitotic chromosome folding
In vivo requirements for rDNA chromosome condensation reveal two cell-cycle-regulated pathways for mitotic chromosome folding
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DOI：
10.1101/gad.1150404
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发表时间：
2004-01-01
影响因子：
10.5
通讯作者：
Koshland, D
中科院分区：
文献类型：
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作者：
Lavoie, BD;Hogan, E;Koshland, D
染色体凝聚在维持遗传完整性方面起着至关重要的作用。利用遗传学、细胞生物学和生物化学的方法，我们区分了两种细胞周期调节的酵母细胞染色体凝聚途径。从G(2)到中期，我们证明了类似于1-Mb rDNA阵列的凝聚是一个多步骤的过程，并描述了染色体折叠中依赖凝集素的聚集、比对和分辨步骤。我们在功能上定义了进一步的中期后染色体组装成熟步骤，这是在分离过程中维持染色体结构完整性所必需的。这一后期的缩合过程除了凝聚素外，还需要保守的有丝分裂酶Ipl1/aurora，但不依赖于凝集素。与此一致的是，晚期缩合途径是在中期到后期转变过程中启动的，支持粘附素中的从头缩合。突变，并与依赖于Ipl1/aurora的凝聚素磷酸化相关。这些数据提供了对高阶染色体折叠的分子机制的洞察，并表明在有丝分裂过程中需要两条不同的凝聚途径，一条涉及粘附素，另一条涉及Ipl1/aurora，以调节染色体结构。
Chromosome condensation plays an essential role in the maintenance of genetic integrity. Using genetic, cell biological, and biochemical approaches, we distinguish two cell-cycle-regulated pathways for chromosome condensation in budding yeast. From G(2) to metaphase, we show that the condensation of the similar to1-Mb rDNA array is a multistep process, and describe condensin-dependent clustering, alignment, and resolution steps in chromosome folding. We functionally define a further postmetaphase chromosome assembly maturation step that is required for the maintenance of chromosome structural integrity during segregation. This late step in condensation requires the conserved mitotic kinase Ipl1/aurora in addition to condensin, but is independent of cohesin. Consistent with this, the late condensation pathway is initiated during the metaphase-to-anaphase transition, supports de novo condensation in cohesin. mutants, and correlates with the Ipl1/aurora-dependent phosphorylation of condensin. These data provide insight into the molecular mechanisms of higher-order chromosome folding and suggest that two distinct condensation pathways, one involving cohesins and the other Ipl1/aurora, are required to modulate chromosome structure during mitosis.