@article {Chunduri2021.02.22.432226, author = {Narendra Kumar Chunduri and Paul Menges and Vincent Leon Gotsmann and Xiaoxiao Zhang and Balca R. Mardin and Christopher Buccitelli and Jan O. Korbel and Felix Willmund and Maik Kschischo and Markus Raeschle and Zuzana Storchova}, title = {Systems approaches identify the consequences of monosomy in somatic human cells}, elocation-id = {2021.02.22.432226}, year = {2021}, doi = {10.1101/2021.02.22.432226}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Chromosome loss that results in monosomy is detrimental to viability, yet, it is frequently observed in cancers. How cancers survive with monosomy is unknown. Using p53 deficient monosomic cell lines, we found that chromosome loss impairs proliferation and genomic stability. Transcriptome and proteome analysis revealed a partial compensation of the gene dosage changes that mitigates the effects of chromosome loss. Monosomy triggers global gene expression changes that differ from the effects of trisomy. We show that ribosome biogenesis and translation were commonly downregulated in monosomic cells, likely due to haploinsufficiency of ribosomal genes. The ensuing ribosome biogenesis stress triggers the p53 pathway and G1 arrest when TP53 is reintroduced into monosomic cells. Accordingly, impaired ribosome biogenesis and p53 inactivation are associated with monosomy in cancer. Our first systematic study of monosomy in human cells explains why monosomy is so detrimental and how loss of p53 enables its incidence in cancer.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2021/02/23/2021.02.22.432226}, eprint = {https://www.biorxiv.org/content/early/2021/02/23/2021.02.22.432226.full.pdf}, journal = {bioRxiv} }