Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action

Chemogenomic screens were performed in both budding and fission yeasts, allowing for a cross-species comparison of drug–gene interaction networks.Drug–module interactions were more conserved than individual drug–gene interactions.Combination of data from both species can improve drug–module predictions and helps identify a compound's mode of action

Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets

AbstractThe invasive phenotype of glioblastoma multiforme (GBM) is a hallmark of malignant process, yet molecular mechanisms that dictate this locally invasive behavior remain poorly understood. Gene expression profiles of human glioma cells were assessed from laser capture-microdissected GBM cells collected from paired patient tumor cores and white matterinvading cell populations. Changes in gene expression in invading GBM cells were validated by quantitative reverse transcription polymerase chain reaction (QRTPCR) and immunohistochemistry in an independent sample set. QRT-PCR confirmed the differential expression in 19 of 21 genes tested. Immunohistochemical analyses of autotaxin (ATX), ephrin 133, B-cell lymphoma-w (BCLW), and protein tyrosine kinase 2 beta showed them to be expressed in invasive glioma cells. The known GBM markers, insulin-like growth factor binding protein 2 and vimentin, were robustly expressed in the tumor core. A glioma invasion tissue microarray confirmed the expression of ATX and BCLW in invasive cells of tumors of various grades. GBM phenotypic and genotypic heterogeneity is well documented. In this study, we show an additional layer of complexity: transcriptional differences between cells of tumor core and invasive cells located in the brain parenchyma. Gene products supporting invasion may be novel targets for manipulation of brain tumor behavior with consequences on treatment outcome

Colocalization of Mec1 and Mrc1 is sufficient for Rad53 phosphorylation in vivo

In the DNA damage checkpoint, the sensor kinase Mec1 must be activated by Ddc1 or Dpb11. However, Ddc1 and Dpb11 are dispensable for the related replication checkpoint. Instead, colocalization of Mec1 and the replisome component Mrc1 is the minimal signal required to activate the replication checkpoint and allow survival of replication stress