Levels of Ycg1 Limit Condensin Function during the Cell Cycle.
Levels of Ycg1 Limit Condensin Function during the Cell Cycle.
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DOI：
10.1371/journal.pgen.1006216
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发表时间：
2016-07
期刊：
影响因子：
4.5
通讯作者：
Benanti JA
中科院分区：
文献类型：
--
作者：
Doughty TW;Arsenault HE;Benanti JA
During mitosis chromosomes are condensed to facilitate their segregation, through a process mediated by the condensin complex. Although several factors that promote maximal condensin activity during mitosis have been identified, the mechanisms that downregulate condensin activity during interphase are largely unknown. Here, we demonstrate that Ycg1, the Cap-G subunit of budding yeast condensin, is cell cycle-regulated with levels peaking in mitosis and decreasing as cells enter G1 phase. This cyclical expression pattern is established by a combination of cell cycle-regulated transcription and constitutive degradation. Interestingly, overexpression of YCG1 and mutations that stabilize Ycg1 each result in delayed cell-cycle entry and an overall proliferation defect. Overexpression of no other condensin subunit impacts the cell cycle, suggesting that Ycg1 is limiting for condensin complex formation. Consistent with this possibility, we find that levels of intact condensin complex are reduced in G1 phase compared to mitosis, and that increased Ycg1 expression leads to increases in both levels of condensin complex and binding to chromatin in G1. Together, these results demonstrate that Ycg1 levels limit condensin function in interphase cells, and suggest that the association of condensin with chromosomes must be reduced following mitosis to enable efficient progression through the cell cycle. Chromosome conformation is cell cycle-regulated so that chromosomes are highly compacted to facilitate their segregation during mitosis, and decondensed during interphase to facilitate DNA-dependent processes such as replication and transcription. Understanding how chromosomes transition between these different states is important for understanding how cells maintain a stable genome. The condensin complex is an essential five-subunit complex that controls chromosome condensation in all eukaryotes. In this study, we show that expression of the Cap-G/Ycg1 subunit of condensin in budding yeast is cell cycle-regulated, and that its reduced expression during interphase limits condensin function. When this regulation is disrupted, and Ycg1 is constitutively expressed, progression through interphase is delayed. Emerging evidence indicates that individual condensin subunits are also expressed at limiting levels in metazoan cells, which suggests that cell-cycle regulation of an individual condensin subunit is a conserved mechanism that coordinates condensin function with the cell cycle.
