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

Article Article scientifique Article The mRNA export adaptor Yra1 contributes to DNA double-strand break repair through its C-box domain eng 2019-04-05 2019-04-05 author Infantino Valentina 762074 author Tutucci Evelina 0000-0002-1998-7146 683360 author Yeh Martin Noël 703853 author Zihlmann Audrey 696674 author Garcia-Molinero Varinia author Silvano Gargano Géraldine 28556 Département de biologie moléculaire et cellulaire (MOCEL) author Palancade Benoit 0000-0002-3894-9735 author Stutz Françoise 0000-0001-9718-355X 64881 Département de biologie moléculaire et cellulaire (MOCEL) e0206336 10.1371/journal.pone.0206336 30951522 1932-6203 PMC6450643 https://dx.plos.org/10.1371/journal.pone.0206336 <p>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 ubiquiti-nation 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.</p> Dewey 570 Polish Swiss Research Programme PSRP NoCore 183/2010 Swiss National Science Foundation Role of antisense transcription in gene regulation and importance of ubiquitination and sumoylation in mRNA biogenesis and export during yeast cell cycle progression. 153331 CH Projects Canton de Genève 46 Département de biologie cellulaire 165 false PloS one 14 4 601152db-c6df-4ec6-bcb0-cbf7f4e69d2d Article (Published version) Public Article-scientifique-from-unpaywall.pdf 2006532 application/pdf CC BY-4.0 9e1cf59178281d62a4ace043205284b4d029c5ca000eb77af6e7e0814dfb6779 openAccess Faculté des sciences / Section de biologie / Département de biologie cellulaire

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The mRNA export adaptor Yra1 contributes to DNA double-strand break repair through its C-box domain	PloS one			2019	96	42

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Silvano Gargano, Géraldine