Essential Saccharomyces cerevisiae genome instability suppressing genes identify potential human tumor suppressors
Essential Saccharomyces cerevisiae genome instability suppressing genes identify potential human tumor suppressors
复制标题
DOI：
10.1073/pnas.1906921116
复制
发表时间：
2019-08-27
影响因子：
11.1
通讯作者：
Kolodner, Richard D.
中科院分区：
文献类型：
--
作者：
Srivatsan, Anjana;Li, Binzhong;Kolodner, Richard D.
染色体大重排（GCR）在包括癌症在内的人类疾病中起着重要作用。虽然大多数非必需的基因组不稳定性抑制（GIS）基因在酿酒酵母是已知的，突变可能会导致GCR率增加的必要基因还没有得到很好的理解。在这里2 S。酿酒酵母GCR测定用于筛选温度敏感突变体的靶向集合，以鉴定引起GCR率增加的突变。这确定了94个基本GIS（eGIS）基因，其中突变导致GCR率增加，以及38个候选eGIS基因编码eGIS 1蛋白相互作用或家族成员蛋白。TCGA数据分析使用预测编码与S.酿酒酵母eGIS基因的突变显示，在分析的16种癌症中的10种中，影响预测的人类eGIS基因的突变显著富集。
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.