Dissecting the functional links between the mRNA export adaptor Yra1, the E3 ubiquitin ligase Slx5-Slx8 and genome stability

Yra1 is an essential RNA binding protein in S. cerevisiae. The aim of this thesis was to elucidate the function of Yra1 ubiquitination by the STUbL Slx5-Slx8. We examined whether Yra1 ubiquitination by Slx5-Slx8 leads to proteasomal degradation (Chapter 1). Our studies indicate that Yra1 ubiquitination by Slx5-Slx8 does not promote Yra1 degradation. One hypothesis is that Yra1 ubiquitination by Slx5-Slx8 may be important for Yra1 auto-regulation. We could not conclude whether Yra1 ubiquitination by Slx5-Slx8 is important for Yra1 splicing auto-regulation (Chapter 2). We analyzed the effect of Yra1 overexpression (OE) mutants on pathways in which Slx5-Slx8 have been implicated. We analyzed the effect of Yra1 overexpression on the DNA Damage Response (Chapter 3) and on irreparable DSBs (Chapter 4), as well as on Chromosome Segregation (Chapter 5). Overall, this study supports the importance of Yra1 regulation in two pivotal pathways: the DNA Damage Response and the Spindle Positioning.