Unbiased compound-protein interface mapping and prediction of chemoresistance loci through forward genetics in haploid stem cells.

ABSTRACT: Forward genetic screens in haploid mammalian cells have recently emerged as powerful tools for the discovery and investigation of recessive traits. Use of the haploid system provides unique genetic tractability and resolution. Upon positive selection, these screens typically employ analysis of loss-of-function (LOF) alleles and are thus limited to non-essential genes. Many relevant compounds, including anti-cancer therapeutics, however, target essential genes, precluding positive selection of LOF alleles. Here, we asked whether the use of random and saturating chemical mutagenesis might enable screens that identify essential biological targets of toxic compounds. We compare and contrast chemical mutagenesis with insertional mutagenesis. Selecting mutagenized cells with thapsigargin, an inh

SUBMITTER: Horn M 

PROVIDER: S-EPMC5839405 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature