Wei-Shan Hsu, Amit Vas C, Clarke Duncan J
Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, MN, USA.
Present address: Cargill Inc., Wayzata, MN, USA.
Oncotarget. 2019 Jan 8;10(3):263-276. doi: 10.18632/oncotarget.26467.
The condensin complex is a conserved ATPase which promotes the compaction of chromatin during mitosis in eukaryotic cells. Condensin complexes have in addition been reported to contribute to interphase processes including sister chromatid cohesion. It is not understood how condensins specifically become competent to facilitate chromosome condensation in preparation for chromosome segregation in anaphase. Here we describe evidence that core condensin subunits are regulated at the level of protein stability in budding yeast. In particular, Smc2 and Smc4 abundance is cell cycle regulated, peaking at mitosis and falling to low levels in interphase. Smc4 degradation at the end of mitosis is dependent on the Anaphase Promoting Complex/Cyclosome and is mediated by the proteasome. Overproduction of Smc4 results in delayed decondensation, but has a limited ability to promote premature condensation in interphase. Unexpectedly, the Mad2 spindle checkpoint protein is required for mitotic Smc4 degradation. These studies have revealed the novel finding that condensin protein levels are cell cycle regulated and have identified the factors necessary for Smc4 proteolysis.
凝聚素复合体是一种保守的ATP酶，在真核细胞有丝分裂过程中促进染色质的压缩。此外，有报道称凝聚素复合体有助于包括姐妹染色单体黏连在内的间期过程。目前尚不清楚凝聚素如何在有丝分裂后期为染色体分离做准备时，具体具备促进染色体凝聚的能力。在此，我们描述了在芽殖酵母中核心凝聚素亚基在蛋白质稳定性水平上受到调控的证据。特别是，Smc2和Smc4的丰度受细胞周期调控，在有丝分裂时达到峰值，在间期降至低水平。有丝分裂末期Smc4的降解依赖于后期促进复合体/细胞周期体，并由蛋白酶体介导。过量表达Smc4会导致解聚延迟，但在间期促进过早凝聚的能力有限。出乎意料的是，有丝分裂期Smc4的降解需要Mad2纺锤体检查点蛋白。这些研究揭示了凝聚素蛋白水平受细胞周期调控这一新发现，并确定了Smc4蛋白水解所需的因素。
