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

Nat Commun. 2022 Sep 22;13(1):5565. doi: 10.1038/s41467-022-33311-y.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcineurin / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Replication
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Neoplasm Proteins
  • Schizosaccharomyces pombe Proteins* / genetics
  • Schizosaccharomyces pombe Proteins* / metabolism
  • Schizosaccharomyces* / genetics
  • Schizosaccharomyces* / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Cell Cycle Proteins
  • Dma1 protein, S pombe
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Schizosaccharomyces pombe Proteins
  • cytoplasmic linker protein 170
  • Ubiquitin-Protein Ligases
  • Calcineurin