naa a22 4500 528785095 20180924065518.0 cr unu---uuuuu 180924e20130613xx s 000 0 eng 10.3929/ethz-b-000070045 doi 10.1371/journal.pone.0065628 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/70045 Centromere Binding and a Conserved Role in Chromosome Stability for SUMO-Dependent Ubiquitin Ligases [Elektronische Daten] [Loes A. L. van de Pasch, Antony J. Miles, Wilco Nijenhuis, Nathalie A. C. H. Brabers, Dik van Leenen, Philip Lijnzaad, Markus K. Brown, Jimmy Ouellet, Yves Barral, Geert J.P.L. Kops, Frank C. P. Holstege] PLoS ONE Open access ethresearch The Saccharomyces cerevisiae Slx5/8 complex is the founding member of a recently defined class of SUMO-targeted ubiquitin ligases (STUbLs). Slx5/8 has been implicated in genome stability and transcription, but the precise contribution is unclear. To characterise Slx5/8 function, we determined genome-wide changes in gene expression upon loss of either subunit. The majority of mRNA changes are part of a general stress response, also exhibited by mutants of other genome integrity pathways and therefore indicative of an indirect effect on transcription. Genome-wide binding analysis reveals a uniquely centromeric location for Slx5. Detailed phenotype analyses of slx5Δ and slx8Δ mutants show severe mitotic defects that include aneuploidy, spindle mispositioning, fish hooks and aberrant spindle kinetics. This is associated with accumulation of the PP2A regulatory subunit Rts1 at centromeres prior to entry into anaphase. Knockdown of the human STUbL orthologue RNF4 also results in chromosome segregation errors due to chromosome bridges. The study shows that STUbLs have a conserved role in maintenance of chromosome stability and links SUMO-dependent ubiquitination to a centromere-specific function during mitosis. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Pasch Loes A. L. van de joint author Miles Antony J. joint author Nijenhuis Wilco joint author Brabers Nathalie A. C. H. joint author Leenen Dik van joint author Lijnzaad Philip joint author Brown Markus K. joint author Ouellet Jimmy joint author Barral Yves joint author Kops Geert J.P.L. joint author Holstege Frank C. P. joint author PLoS ONE Public Library of Science 8 (6), p. e65628 1932-6203 http://hdl.handle.net/20.500.11850/70045 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/70045 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Pasch Loes A. L. van de joint author ETHRESEARCH 700 1- Miles Antony J. joint author ETHRESEARCH 700 1- Nijenhuis Wilco joint author ETHRESEARCH 700 1- Brabers Nathalie A. C. H. joint author ETHRESEARCH 700 1- Leenen Dik van joint author ETHRESEARCH 700 1- Lijnzaad Philip joint author ETHRESEARCH 700 1- Brown Markus K. joint author ETHRESEARCH 700 1- Ouellet Jimmy joint author ETHRESEARCH 700 1- Barral Yves joint author ETHRESEARCH 700 1- Kops Geert J.P.L. joint author ETHRESEARCH 700 1- Holstege Frank C. P. joint author ETHRESEARCH 773 0- PLoS ONE Public Library of Science 8 (6), p. e65628 1932-6203 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access