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A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers

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  • Christopher D. Putnam

    (Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego
    University of California School of Medicine, San Diego)

  • Anjana Srivatsan

    (Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego)

  • Rahul V. Nene

    (Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego)

  • Sandra L. Martinez

    (Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego)

  • Sarah P. Clotfelter

    (Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego)

  • Sara N. Bell

    (Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego)

  • Steven B. Somach

    (Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego)

  • Jorge E.S. de Souza

    (Instituto de Bioinformática e Biotecnologia
    Instituto Metrópole Digital, UFRN)

  • André F. Fonseca

    (Instituto do Cérebro, UFRN)

  • Sandro J. de Souza

    (Instituto do Cérebro, UFRN)

  • Richard D. Kolodner

    (Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego
    University of California School of Medicine, San Diego
    Moores-UCSD Cancer Center, University of California School of Medicine, San Diego
    Institute of Genomic Medicine, University of California School of Medicine, San Diego)

Abstract

Gross chromosomal rearrangements (GCRs) play an important role in human diseases, including cancer. The identity of all Genome Instability Suppressing (GIS) genes is not currently known. Here multiple Saccharomyces cerevisiae GCR assays and query mutations were crossed into arrays of mutants to identify progeny with increased GCR rates. One hundred eighty two GIS genes were identified that suppressed GCR formation. Another 438 cooperatively acting GIS genes were identified that were not GIS genes, but suppressed the increased genome instability caused by individual query mutations. Analysis of TCGA data using the human genes predicted to act in GIS pathways revealed that a minimum of 93% of ovarian and 66% of colorectal cancer cases had defects affecting one or more predicted GIS gene. These defects included loss-of-function mutations, copy-number changes associated with reduced expression, and silencing. In contrast, acute myeloid leukaemia cases did not appear to have defects affecting the predicted GIS genes.

Suggested Citation

  • Christopher D. Putnam & Anjana Srivatsan & Rahul V. Nene & Sandra L. Martinez & Sarah P. Clotfelter & Sara N. Bell & Steven B. Somach & Jorge E.S. de Souza & André F. Fonseca & Sandro J. de Souza & Ri, 2016. "A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11256
    DOI: 10.1038/ncomms11256
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