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

Stutz, F.; Infantino, V.; Tutucci, E.; Yeh Martin, N.; Zihlmann, A.; Garcia-Molinero, V.; Silvano, G.; Palancade, B.

doi:10.1101/441980

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bioRxiv · 10.1101/441980

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

Stutz, F.·Infantino, V.·Tutucci, E.·Yeh Martin, N.·Zihlmann, A.·Garcia-Molinero, V.·Silvano, G.·Palancade, B.

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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. Interestingly, 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. Here we show that Yra1 binds an HO-induced irreparable DSB. 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. Unexpectedly, while the Yra1 C-box is essential, Yra1 sumoylation and/or ubiquitination are dispensable in this process.

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Stutz, F., Infantino, V., Tutucci, E., Yeh Martin, N., Zihlmann, A., Garcia-Molinero, V., Silvano, G., Palancade, B.. 2018-10-12. The mRNA export adaptor Yra1 contributes to DNA double-strand break repair through its C-box domain. https://doi.org/10.1101/441980

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