The mRNA export adaptor Yra1 contributes to DNA double-strand break repair through its C-box domain

PLoS One. 2019 Apr 5;14(4):e0206336. doi: 10.1371/journal.pone.0206336. eCollection 2019.

Abstract

Yra1 is an mRNA export adaptor involved in mRNA biogenesis and export in S. cerevisiae. Yra1 overexpression was recently shown to promote accumulation of DNA:RNA hybrids favoring DNA double strand breaks (DSB), cell senescence and telomere shortening, via an unknown mechanism. Yra1 was also identified at an HO-induced DSB and Yra1 depletion causes defects in DSB repair. Previous work from our laboratory showed that Yra1 ubiquitination by Tom1 is important for mRNA export. Here, we found that Yra1 is also ubiquitinated by the SUMO-targeted ubiquitin ligases Slx5-Slx8 implicated in the interaction of irreparable DSB with nuclear pores. We further show that Yra1 binds an HO-induced irreparable DSB in a process dependent on resection. Importantly, a Yra1 mutant lacking the evolutionarily conserved C-box is not recruited to an HO-induced irreparable DSB and becomes lethal under DSB induction in a HO-cut reparable system. Together, the data provide evidence that Yra1 plays a crucial role in DSB repair via homologous recombination. While Yra1 sumoylation and/or ubiquitination are dispensable, the Yra1 C-box region is essential in this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Breaks, Double-Stranded*
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Domains
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Recombinational DNA Repair*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • DNA, Fungal
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • YRA1 protein, S cerevisiae
  • Slx8 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • Slx5 protein, S cerevisiae

Grant support

This work was funded by NCCR ‘Frontiers in Genetics’ (fellowship to VI), the Swiss National Science Foundation (grant no 31003A 153331 to FS), Polish Swiss Research Programme PSRP NoCore (183/2010 to FS), iGE3 and the Canton of Geneva. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.