Ubiquitination of CLIP-170 family protein restrains polarized growth upon DNA replication stress

• Published in: Nature communications Vol. 13; no. 1; p. 5565
• Main Authors: Wang, Xi, Zheng, Fan, Yi, Yuan-yuan, Wang, Gao-yuan, Hong, Li-xin, McCollum, Dannel, Fu, Chuanhai, Wang, Yamei, Jin, Quan-wen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 14/63; 38/1; 38/35; 631/80/85/2361; 631/80/86/2371; 82/29; 82/58; 96/31; Calcineurin; Calcineurin - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA damage; DNA Replication; Fission; Homology; Humanities and Social Sciences; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules; Microtubules - metabolism; multidisciplinary; Neoplasm Proteins; Polarity; Proteins; Replication; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Science; Science (multidisciplinary); Stress; Tracking; Ubiquitin; Ubiquitin-protein ligase; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ubiquitination; Yeast; Yeasts
• ISSN: 2041-1723; 2041-1723
• 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. The microtubule plus-end tracking protein Tip1 regulates microtubule dynamics and polar growth in fission yeast. Here the authors link the ubiquitination of Tip1 by ubiquitin ligase Dma1 to polarized growth inhibition upon DNA replication stress.