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Systems approaches identify the consequences of monosomy in somatic human cells

Author

Listed:
  • Narendra Kumar Chunduri

    (TU Kaiserslautern)

  • Paul Menges

    (TU Kaiserslautern)

  • Xiaoxiao Zhang

    (University of Applied Sciences Koblenz)

  • Angela Wieland

    (TU Kaiserslautern)

  • Vincent Leon Gotsmann

    (TU Kaiserslautern)

  • Balca R. Mardin

    (European Molecular Biology Laboratory (EMBL))

  • Christopher Buccitelli

    (European Molecular Biology Laboratory (EMBL))

  • Jan O. Korbel

    (European Molecular Biology Laboratory (EMBL))

  • Felix Willmund

    (TU Kaiserslautern)

  • Maik Kschischo

    (University of Applied Sciences Koblenz)

  • Markus Raeschle

    (TU Kaiserslautern)

  • Zuzana Storchova

    (TU Kaiserslautern)

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 find that chromosome loss impairs proliferation and genomic stability. Transcriptome and proteome analysis demonstrates reduced expression of genes encoded on the monosomes, which is partially compensated in some cases. Monosomy also induces global changes in gene expression. Pathway enrichment analysis reveals that genes involved in ribosome biogenesis and translation are downregulated in all monosomic cells analyzed. Consistently, monosomies display defects in protein synthesis and ribosome assembly. We further show that monosomies are incompatible with p53 expression, likely due to defects in ribosome biogenesis. Accordingly, impaired ribosome biogenesis and p53 inactivation are associated with monosomy in cancer. Our systematic study of monosomy in human cells explains why monosomy is so detrimental and reveals the importance of p53 for monosomy occurrence in cancer.

Suggested Citation

  • Narendra Kumar Chunduri & Paul Menges & Xiaoxiao Zhang & Angela Wieland & Vincent Leon Gotsmann & Balca R. Mardin & Christopher Buccitelli & Jan O. Korbel & Felix Willmund & Maik Kschischo & Markus Ra, 2021. "Systems approaches identify the consequences of monosomy in somatic human cells," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25288-x
    DOI: 10.1038/s41467-021-25288-x
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    Cited by:

    1. Johanna Zerbib & Marica Rosaria Ippolito & Yonatan Eliezer & Giuseppina Feudis & Eli Reuveni & Anouk Savir Kadmon & Sara Martin & Sonia Viganò & Gil Leor & James Berstler & Julia Muenzner & Michael Mü, 2024. "Human aneuploid cells depend on the RAF/MEK/ERK pathway for overcoming increased DNA damage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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