IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10754.html
   My bibliography  Save this article

The presence of extra chromosomes leads to genomic instability

Author

Listed:
  • Verena Passerini

    (Max Planck Institute of Biochemistry, Am Klopferspitz 18
    Center for Integrated Protein Science Munich)

  • Efrat Ozeri-Galai

    (The Alexander Silberman Institute of Life Sciences, Edmond J. Safra Campus, Givat-Ram)

  • Mirjam S. de Pagter

    (Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100)

  • Neysan Donnelly

    (Max Planck Institute of Biochemistry, Am Klopferspitz 18)

  • Sarah Schmalbrock

    (Max Planck Institute of Biochemistry, Am Klopferspitz 18)

  • Wigard P. Kloosterman

    (Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100)

  • Batsheva Kerem

    (The Alexander Silberman Institute of Life Sciences, Edmond J. Safra Campus, Givat-Ram)

  • Zuzana Storchová

    (Max Planck Institute of Biochemistry, Am Klopferspitz 18
    Center for Integrated Protein Science Munich
    Technical University Kaiserslautern, Paul-Ehrlich Strasse, Building 24)

Abstract

Aneuploidy is a hallmark of cancer and underlies genetic disorders characterized by severe developmental defects, yet the molecular mechanisms explaining its effects on cellular physiology remain elusive. Here we show, using a series of human cells with defined aneuploid karyotypes, that gain of a single chromosome increases genomic instability. Next-generation sequencing and SNP-array analysis reveal accumulation of chromosomal rearrangements in aneuploids, with break point junction patterns suggestive of replication defects. Trisomic and tetrasomic cells also show increased DNA damage and sensitivity to replication stress. Strikingly, we find that aneuploidy-induced genomic instability can be explained by the reduced expression of the replicative helicase MCM2-7. Accordingly, restoring near-wild-type levels of chromatin-bound MCM helicase partly rescues the genomic instability phenotypes. Thus, gain of chromosomes triggers replication stress, thereby promoting genomic instability and possibly contributing to tumorigenesis.

Suggested Citation

  • Verena Passerini & Efrat Ozeri-Galai & Mirjam S. de Pagter & Neysan Donnelly & Sarah Schmalbrock & Wigard P. Kloosterman & Batsheva Kerem & Zuzana Storchová, 2016. "The presence of extra chromosomes leads to genomic instability," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10754
    DOI: 10.1038/ncomms10754
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10754
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10754?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Lorenza Garribba & Giuseppina De Feudis & Valentino Martis & Martina Galli & Marie Dumont & Yonatan Eliezer & René Wardenaar & Marica Rosaria Ippolito & Divya Ramalingam Iyer & Andréa E. Tijhuis & Dia, 2023. "Short-term molecular consequences of chromosome mis-segregation for genome stability," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. M. Kyle Cromer & Valentin V. Barsan & Erich Jaeger & Mengchi Wang & Jessica P. Hampton & Feng Chen & Drew Kennedy & Jenny Xiao & Irina Khrebtukova & Ana Granat & Tiffany Truong & Matthew H. Porteus, 2022. "Ultra-deep sequencing validates safety of CRISPR/Cas9 genome editing in human hematopoietic stem and progenitor cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Revati Darp & Marc A. Vittoria & Neil J. Ganem & Craig J. Ceol, 2022. "Oncogenic BRAF induces whole-genome doubling through suppression of cytokinesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10754. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.