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Cellular response upon proliferation in the presence of an active mitotic checkpoint.
Life Science Alliance ( IF 4.4 ) Pub Date : 2019-05-08 , DOI: 10.26508/lsa.201900380
Andrea Corno 1 , Elena Chiroli 1 , Fridolin Gross 1 , Claudio Vernieri 1, 2 , Vittoria Matafora 1 , Stefano Maffini 3 , Marco Cosentino Lagomarsino 1, 4 , Angela Bachi 1 , Andrea Ciliberto 5, 6
Affiliation  

Eukaryotic cells treated with microtubule-targeting agents activate the spindle assembly checkpoint to arrest in mitosis and prevent chromosome mis-segregation. A fraction of mitotically arrested cells overcomes the block and proliferates even under persistent checkpoint-activating conditions. Here, we asked what allows proliferation in such unfavourable conditions. We report that yeast cells are delayed in mitosis at each division, implying that their spindle assembly checkpoint remains responsive. The arrest causes their cell cycle to be elongated and results in a size increase. Growth saturates at mitosis and correlates with the repression of various factors involved in translation. Contrary to unperturbed cells, growth of cells with an active checkpoint requires Cdh1. This peculiar cell cycle correlates with global changes in protein expression whose signatures partly overlap with the environmental stress response. Hence, cells dividing with an active checkpoint develop recognisable specific traits that allow them to successfully complete cell division notwithstanding a constant mitotic checkpoint arrest. These properties distinguish them from unperturbed cells. Our observation may have implications for the identification of new therapeutic windows and targets in tumors.

中文翻译:

在有丝分裂检查点存在下细胞增殖后的细胞反应。

用微管靶向剂处理的真核细胞激活纺锤体装配检查点,使其停滞在有丝分裂中并防止染色体错误分离。即使在持续的检查点激活条件下,一小部分有丝分裂阻滞的细胞也能克服该障碍并增殖。在这里,我们问到在这种不利条件下是什么导致了扩散。我们报告酵母细胞在每个分裂的有丝分裂被延迟,这意味着它们的纺锤体组装检查点仍然是有反应的。停滞使它们的细胞周期延长并导致大小增加。生长在有丝分裂时达到饱和,并与翻译中涉及的各种因素的抑制相关。与不受干扰的细胞相反,具有活跃检查点的细胞生长需要Cdh1。这种特殊的细胞周期与蛋白质表达的整体变化有关,其整体特征与环境应激反应部分重叠。因此,用有活性的检查点分裂的细胞会形成可识别的特定性状,即使有丝分裂检查点停滞不断,它们也能成功完成细胞分裂。这些特性将它们与不受干扰的细胞区分开来。我们的观察结果可能对鉴定肿瘤中新的治疗窗口和靶标有影响。
更新日期:2020-08-21
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