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Ubiquitin proteomics reveals critical targets of the Nse1 RING domain in rDNA and genome stability

ABSTRACT: Ubiquitination controls most cellular processes, and its deregulation is associated to many pathologies. The Nse1 subunit in the Smc5/6 complex contains a RING domain with ubiquitin E3 ligase activity and important functions in genome integrity. However, Nse1-dependent ubiquitin targets remain largely unknown. Here, we use label-free quantitative proteomics to analyse the nuclear ubiquitinome of nse1 RING mutant cells. Our results show that Nse1 impacts on the ubiquitination of several proteins involved in DNA damage tolerance, ribosome biogenesis and metabolism that, importantly, extend beyond canonical functions of the Smc5/6 complex in chromosome segregation. In addition, our analysis uncovers an unexpected connection between Nse1 and Pol I ubiquitination. Specifically, Nse1 promotes the ubiquitination of K408 and K410 in Rpa190, the largest subunit of Pol I, to induce its degradation. We propose that this mechanism contributes to Smc5/6-dependent rDNA disjunction in response to transcriptional elongation defects.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Pilar Ximenez-Embun

LAB HEAD: Javier Muñoz

PROVIDER: PXD028669 | Pride | 2023-05-05

REPOSITORIES: Pride

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