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

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 iden...

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Autores principales: Putnam, Christopher D., Srivatsan, Anjana, Nene, Rahul V., Martinez, Sandra L., Clotfelter, Sarah P., Bell, Sara N., Somach, Steven B., E.S. de Souza, Jorge, Fonseca, André F., de Souza, Sandro J., Kolodner, Richard D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833866/
https://www.ncbi.nlm.nih.gov/pubmed/27071721
http://dx.doi.org/10.1038/ncomms11256
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author Putnam, Christopher D.
Srivatsan, Anjana
Nene, Rahul V.
Martinez, Sandra L.
Clotfelter, Sarah P.
Bell, Sara N.
Somach, Steven B.
E.S. de Souza, Jorge
Fonseca, André F.
de Souza, Sandro J.
Kolodner, Richard D.
author_facet Putnam, Christopher D.
Srivatsan, Anjana
Nene, Rahul V.
Martinez, Sandra L.
Clotfelter, Sarah P.
Bell, Sara N.
Somach, Steven B.
E.S. de Souza, Jorge
Fonseca, André F.
de Souza, Sandro J.
Kolodner, Richard D.
author_sort Putnam, Christopher D.
collection PubMed
description 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.
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spelling pubmed-48338662016-05-02 A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers Putnam, Christopher D. Srivatsan, Anjana Nene, Rahul V. Martinez, Sandra L. Clotfelter, Sarah P. Bell, Sara N. Somach, Steven B. E.S. de Souza, Jorge Fonseca, André F. de Souza, Sandro J. Kolodner, Richard D. Nat Commun Article 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. Nature Publishing Group 2016-04-13 /pmc/articles/PMC4833866/ /pubmed/27071721 http://dx.doi.org/10.1038/ncomms11256 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Putnam, Christopher D.
Srivatsan, Anjana
Nene, Rahul V.
Martinez, Sandra L.
Clotfelter, Sarah P.
Bell, Sara N.
Somach, Steven B.
E.S. de Souza, Jorge
Fonseca, André F.
de Souza, Sandro J.
Kolodner, Richard D.
A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers
title A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers
title_full A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers
title_fullStr A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers
title_full_unstemmed A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers
title_short A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers
title_sort genetic network that suppresses genome rearrangements in saccharomyces cerevisiae and contains defects in cancers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833866/
https://www.ncbi.nlm.nih.gov/pubmed/27071721
http://dx.doi.org/10.1038/ncomms11256
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