Institute of Biochemistry, Biology Department, ETH Zurich, 8093 Zurich, Switzerland.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0379 Oslo, Norway.
Cell. 2018 Oct 18;175(3):780-795.e15. doi: 10.1016/j.cell.2018.09.012. Epub 2018 Oct 11.
During mitosis, chromatin condensation shapes chromosomes as separate, rigid, and compact sister chromatids to facilitate their segregation. Here, we show that, unlike wild-type yeast chromosomes, non-chromosomal DNA circles and chromosomes lacking a centromere fail to condense during mitosis. The centromere promotes chromosome condensation strictly in cis through recruiting the kinases Aurora B and Bub1, which trigger the autonomous condensation of the entire chromosome. Shugoshin and the deacetylase Hst2 facilitated spreading the condensation signal to the chromosome arms. Targeting Aurora B to DNA circles or centromere-ablated chromosomes or releasing Shugoshin from PP2A-dependent inhibition bypassed the centromere requirement for condensation and enhanced the mitotic stability of DNA circles. Our data indicate that yeast cells license the chromosome-autonomous condensation of their chromatin in a centromere-dependent manner, excluding from this process non-centromeric DNA and thereby inhibiting their propagation.
在有丝分裂过程中,染色质凝聚将染色体塑造成独立、刚性和紧凑的姐妹染色单体,以促进其分离。在这里,我们表明,与野生型酵母染色体不同,非染色体 DNA 环和没有着丝粒的染色体在有丝分裂过程中不会发生凝聚。着丝粒通过招募激酶 Aurora B 和 Bub1 在顺式严格促进染色体凝聚,这触发了整个染色体的自主凝聚。Shugoshin 和去乙酰化酶 Hst2 有助于将凝聚信号传播到染色体臂上。将 Aurora B 靶向 DNA 环或着丝粒缺失的染色体,或从 PP2A 依赖性抑制中释放 Shugoshin,可以绕过着丝粒对凝聚的要求,并增强 DNA 环的有丝分裂稳定性。我们的数据表明,酵母细胞以依赖着丝粒的方式许可其染色质的染色体自主凝聚,从而排除非着丝粒 DNA 参与该过程,从而抑制其复制。