State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, 361102, Fujian, China.
School of Life Sciences, University of Science and Technology of China, Hefei, 230026, Anhui, China.
Nat Commun. 2022 Sep 22;13(1):5565. doi: 10.1038/s41467-022-33311-y.
Microtubules play a crucial role during the establishment and maintenance of cell polarity. In fission yeast cells, the microtubule plus-end tracking proteins (+TIPs) (including the CLIP-170 homologue Tip1) regulate microtubule dynamics and also transport polarity factors to the cell cortex. Here, we show that the E3 ubiquitin ligase Dma1 plays an unexpected role in controlling polarized growth through ubiquitinating Tip1. Dma1 colocalizes with Tip1 to cortical sites at cell ends, and is required for ubiquitination of Tip1. Although the absence of dma1 does not cause apparent polar growth defects in vegetatively growing cells, Dma1-mediated Tip1 ubiquitination is required to restrain polar growth upon DNA replication stress. This mechanism is distinct from the previously recognized calcineurin-dependent inhibition of polarized growth. In this work, we establish a link between Dma1-mediated Tip1 ubiquitination and DNA replication or DNA damage checkpoint-dependent inhibition of polarized growth in fission yeast.
微管在建立和维持细胞极性方面起着至关重要的作用。在裂殖酵母细胞中，微管末端追踪蛋白（+TIPs）（包括 CLIP-170 同源物 Tip1）调节微管动力学，并将极性因子运输到质膜。在这里，我们发现 E3 泛素连接酶 Dma1 通过泛素化 Tip1 来控制极化生长的意外作用。Dma1 与 Tip1 共定位于细胞末端的皮质部位，并且 Tip1 的泛素化需要 Dma1。尽管 dma1 的缺失不会导致营养生长细胞中明显的极性生长缺陷，但 Dma1 介导的 Tip1 泛素化对于抑制 DNA 复制应激时的极性生长是必需的。这种机制与先前认识到的钙调神经磷酸酶依赖性抑制极性生长不同。在这项工作中，我们在裂殖酵母中建立了 Dma1 介导的 Tip1 泛素化与 DNA 复制或 DNA 损伤检查点依赖性抑制极性生长之间的联系。
