Haspin Modulates the G2/M Transition Delay in Response to Polarization Failures in Budding Yeast.

Haspin Modulates the G2/M Transition Delay in Response to Polarization Failures in Budding Yeast.
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DOI:
10.3389/fcell.2020.625717
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发表时间:
2020
影响因子:
5.5
通讯作者:
Muzi-Falconi M
Muzi-Falconi M
中科院分区:
生物学2区
文献类型:
--
作者:
Galli M;Diani L;Quadri R;Nespoli A;Galati E;Panigada D;Plevani P;Muzi-Falconi M

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通过细胞极化打破对称性是酿酒酵母细胞周期的一个精致要求,因为它允许芽的萌发和生长。这一过程是基于细胞周期中最初萌芽部位和芽尖形成的极性簇的形成,这总体上促进了芽的释放和生长。鉴于这一过程的极端相关性,一种被称为形态发生检查点的监测机制已经进化出来,以协调芽的形成和细胞周期的进展,在存在形态发生问题的情况下延迟有丝分裂。非典型蛋白激酶haspin负责组蛋白H3-T3的磷酸化,在酵母中负责有丝分裂中的极性簇的分解。在这里,我们报告了haspin在极性侮辱反应中对形态发生检查点的调节中的一个新角色。特别是,我们发现缺乏haspin原基因Alk1的细胞即使在没有芽的情况下也无法实现持续的检查点激活和进入有丝分裂。在碱性Δ细胞中,我们报告了CDC28-Y19的磷酸化水平降低,这是由于MIH1磷酸酶的过早激活所致。总体而言,这项工作中提供的数据将酵母haspin定义为酿酒酵母中形态发生检查点的一个新的调节器,在那里它监控极性的建立,并将出芽与G2/M细胞周期转变联系在一起。
Symmetry breaking by cellular polarization is an exquisite requirement for the cell-cycle of Saccharomyces cerevisiae cells, as it allows bud emergence and growth. This process is based on the formation of polarity clusters at the incipient bud site, first, and the bud tip later in the cell-cycle, that overall promote bud emission and growth. Given the extreme relevance of this process, a surveillance mechanism, known as the morphogenesis checkpoint, has evolved to coordinate the formation of the bud and cell cycle progression, delaying mitosis in the presence of morphogenetic problems. The atypical protein kinase haspin is responsible for histone H3-T3 phosphorylation and, in yeast, for resolution of polarity clusters in mitosis. Here, we report a novel role for haspin in the regulation of the morphogenesis checkpoint in response to polarity insults. Particularly, we show that cells lacking the haspin ortholog Alk1 fail to achieve sustained checkpoint activation and enter mitosis even in the absence of a bud. In alk1Δ cells, we report a reduced phosphorylation of Cdc28-Y19, which stems from a premature activation of the Mih1 phosphatase. Overall, the data presented in this work define yeast haspin as a novel regulator of the morphogenesis checkpoint in Saccharomyces cerevisiae, where it monitors polarity establishment and it couples bud emergence to the G2/M cell cycle transition.
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