Centromere Binding and a Conserved Role in Chromosome Stability for SUMO-Dependent Ubiquitin Ligases
| Autor: | Nathalie Brabers, Jimmy Ouellet, Antony J. Miles, Philip Lijnzaad, Yves Barral, Markus K. Brown, Geert J. P. L. Kops, Loes A.L. van de Pasch, Wilco Nijenhuis, Frank C. P. Holstege, Dik van Leenen |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Microarrays
Gene Expression lcsh:Medicine Yeast and Fungal Models Biochemistry Chromosome segregation 0302 clinical medicine Ubiquitin Molecular Cell Biology Protein Phosphatase 2 lcsh:Science Anaphase Genetics 0303 health sciences Multidisciplinary biology Chromosome Biology Chromosome Mapping Genomics Functional Genomics Nucleic acids Phenotype Small Ubiquitin-Related Modifier Proteins Genome Fungal Cell Division Plasmids Protein Binding Research Article Saccharomyces cerevisiae Proteins Ubiquitin-Protein Ligases Centromere DNA repair Saccharomyces cerevisiae Spindle Apparatus Genomic Instability 03 medical and health sciences Model Organisms Stress Physiological Chromosomal Instability DNA-binding proteins Mitosis Biology Metaphase 030304 developmental biology lcsh:R Chromosome Proteins Computational Biology DNA Aneuploidy Spindle apparatus Mutation biology.protein lcsh:Q Genome Expression Analysis 030217 neurology & neurosurgery Gene Deletion |
| Zdroj: | PLoS ONE, Vol 8, Iss 6, p e65628 (2013) PloS one PLoS ONE PLoS ONE, 8 (6) |
| ISSN: | 1932-6203 |
| DOI: | 10.3929/ethz-b-000070045 |
| Popis: | 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. PLoS ONE, 8 (6) ISSN:1932-6203 |
| Databáze: | OpenAIRE |
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