Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Systems approaches identify the consequences of monosomy in somatic human cells

Narendra Kumar Chunduri, Paul Menges, Vincent Leon Gotsmann, Xiaoxiao Zhang, Balca R. Mardin, Christopher Buccitelli, Jan O. Korbel, View ORCID ProfileFelix Willmund, Maik Kschischo, Markus Raeschle, Zuzana Storchova
doi: https://doi.org/10.1101/2021.02.22.432226
Narendra Kumar Chunduri
1Dept. of Molecular Genetics, TU Kaiserslautern, Paul-Ehrlich-Strasse 24, 67663 Kaiserslautern, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul Menges
1Dept. of Molecular Genetics, TU Kaiserslautern, Paul-Ehrlich-Strasse 24, 67663 Kaiserslautern, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincent Leon Gotsmann
2Group Genetics of Eukaryotes, TU Kaiserslautern, Paul-Ehrlich-Strasse 23, 67663 Kaiserslautern, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoxiao Zhang
3University of Applied Sciences Koblenz, Joseph-Rovan-Allee 2, Remagen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Balca R. Mardin
4European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117, Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher Buccitelli
4European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117, Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jan O. Korbel
4European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstr. 1, 69117, Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Felix Willmund
2Group Genetics of Eukaryotes, TU Kaiserslautern, Paul-Ehrlich-Strasse 23, 67663 Kaiserslautern, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Felix Willmund
Maik Kschischo
3University of Applied Sciences Koblenz, Joseph-Rovan-Allee 2, Remagen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Markus Raeschle
1Dept. of Molecular Genetics, TU Kaiserslautern, Paul-Ehrlich-Strasse 24, 67663 Kaiserslautern, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zuzana Storchova
1Dept. of Molecular Genetics, TU Kaiserslautern, Paul-Ehrlich-Strasse 24, 67663 Kaiserslautern, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: storchova@bio.uni-kl.de
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted February 23, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Systems approaches identify the consequences of monosomy in somatic human cells
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Systems approaches identify the consequences of monosomy in somatic human cells
Narendra Kumar Chunduri, Paul Menges, Vincent Leon Gotsmann, Xiaoxiao Zhang, Balca R. Mardin, Christopher Buccitelli, Jan O. Korbel, Felix Willmund, Maik Kschischo, Markus Raeschle, Zuzana Storchova
bioRxiv 2021.02.22.432226; doi: https://doi.org/10.1101/2021.02.22.432226
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Systems approaches identify the consequences of monosomy in somatic human cells
Narendra Kumar Chunduri, Paul Menges, Vincent Leon Gotsmann, Xiaoxiao Zhang, Balca R. Mardin, Christopher Buccitelli, Jan O. Korbel, Felix Willmund, Maik Kschischo, Markus Raeschle, Zuzana Storchova
bioRxiv 2021.02.22.432226; doi: https://doi.org/10.1101/2021.02.22.432226

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Systems Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (2633)
  • Biochemistry (5221)
  • Bioengineering (3643)
  • Bioinformatics (15711)
  • Biophysics (7213)
  • Cancer Biology (5593)
  • Cell Biology (8045)
  • Clinical Trials (138)
  • Developmental Biology (4735)
  • Ecology (7462)
  • Epidemiology (2059)
  • Evolutionary Biology (10520)
  • Genetics (7698)
  • Genomics (10082)
  • Immunology (5148)
  • Microbiology (13823)
  • Molecular Biology (5354)
  • Neuroscience (30577)
  • Paleontology (211)
  • Pathology (871)
  • Pharmacology and Toxicology (1519)
  • Physiology (2234)
  • Plant Biology (4983)
  • Scientific Communication and Education (1036)
  • Synthetic Biology (1379)
  • Systems Biology (4130)
  • Zoology (803)