title: Global analysis of genome, transcriptome and proteome reveals the response to aneuploidy in human cells.
abstract: Extra chromosome copies markedly alter the physiology of eukaryotic cells, but the underlying reasons are not well understood. We created human trisomic and tetrasomic cell lines and determined the quantitative changes in their transcriptome and proteome in comparison with their diploid counterparts. We found that whereas transcription levels reflect the chromosome copy number changes, the abundance of some proteins, such as subunits of protein complexes and protein kinases, is reduced toward diploid levels. Furthermore, using the quantitative data we investigated the changes of cellular pathways in response to aneuploidy. This analysis revealed specific and uniform alterations in pathway regulation in cells with extra chromosomes. For example, the DNA and RNA metabolism pathways were downregulated, whereas several pathways such as energy metabolism, membrane metabolism and lysosomal pathways were upregulated. In particular, we found that the p62-dependent selective autophagy is activated in the human trisomic and tetrasomic cells. Our data present the first broad proteomic analysis of human cells with abnormal karyotypes and suggest a uniform cellular response to the presence of an extra chromosome.
authors.affiliation: Group of Maintenance of Genome Stability, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Stingele
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stoehr
authors.forename: Karolina
authors.initials: K
authors.lastname: Peplowska
authors.forename: Jürgen
authors.initials: J
authors.lastname: Cox
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Storchova
mesh_terms: D000782:Aneuploidy; D001343:Autophagy / Q000235:genetics; D002460:Cell Line; D002877:Chromosomes, Human / Q000235:genetics; D004247:DNA / Q000235:genetics; D016678:Genome / Q000235:genetics*; D006801:Humans; D021122:Protein Subunits / Q000378:metabolism; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058670:Tetrasomy / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*; D014314:Trisomy / Q000235:genetics
chemical_list: D021122:Protein Subunits; D020543:Proteome; D012333:RNA, Messenger; D004247:DNA