Essential Saccharomyces cerevisiae genome instability suppressing genes identify potential human tumor suppressors

Proc Natl Acad Sci U S A. 2019 Aug 27;116(35):17377-17382. doi: 10.1073/pnas.1906921116. Epub 2019 Aug 13.

Abstract

Gross Chromosomal Rearrangements (GCRs) play an important role in human diseases, including cancer. Although most of the nonessential Genome Instability Suppressing (GIS) genes in Saccharomyces cerevisiae are known, the essential genes in which mutations can cause increased GCR rates are not well understood. Here 2 S. cerevisiae GCR assays were used to screen a targeted collection of temperature-sensitive mutants to identify mutations that caused increased GCR rates. This identified 94 essential GIS (eGIS) genes in which mutations cause increased GCR rates and 38 candidate eGIS genes that encode eGIS1 protein-interacting or family member proteins. Analysis of TCGA data using the human genes predicted to encode the proteins and protein complexes implicated by the S. cerevisiae eGIS genes revealed a significant enrichment of mutations affecting predicted human eGIS genes in 10 of the 16 cancers analyzed.

Keywords: cancer; chromosome dynamics and replication; genome instability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Damage
  • Genes, Suppressor*
  • Genome, Fungal*
  • Genomic Instability*
  • Humans
  • Mutation
  • Neoplasms / genetics*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Tumor Suppressor Proteins