PT  - JOURNAL ARTICLE
AU  - Narendra Kumar Chunduri
AU  - Paul Menges
AU  - Vincent Leon Gotsmann
AU  - Xiaoxiao Zhang
AU  - Balca R. Mardin
AU  - Christopher Buccitelli
AU  - Jan O. Korbel
AU  - Felix Willmund
AU  - Maik Kschischo
AU  - Markus Raeschle
AU  - Zuzana Storchova
TI  - Systems approaches identify the consequences of monosomy in somatic human cells
AID  - 10.1101/2021.02.22.432226
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.22.432226
4099  - http://biorxiv.org/content/early/2021/02/23/2021.02.22.432226.short
4100  - http://biorxiv.org/content/early/2021/02/23/2021.02.22.432226.full
AB  - 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.