GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Paulsen et al. (2009) Genome stability gamma-H2AX phosphorylation and DNA contentHeLaH. sapiens


Signaling pathways that respond to DNA damage are essential for the maintenance of genome stability and are linked to many diseases, including cancer. Here, a genome-wide siRNA screen was employed to identify additional genes involved in genome stabilization by monitoring phosphorylation of the histone variant H2AX, an early mark of DNA damage. We identified hundreds of genes whose downregulation led to elevated levels of H2AX phosphorylation (gammaH2AX) and revealed links to cellular complexes and to genes with unclassified functions. We demonstrate a widespread role for mRNA-processing factors in preventing DNA damage, which in some cases is caused by aberrant RNA-DNA structures. Furthermore, we connect increased gammaH2AX levels to the neurological disorder Charcot-Marie-Tooth (CMT) syndrome, and we find a role for several CMT proteins in the DNA-damage response. These data indicate that preservation of genome stability is mediated by a larger network of biological processes than previously appreciated.

Screen details

Stable Id: GR00053-A
Screen title: Genome stability
Assay: gamma-H2AX phosphorylation and DNA content
Method: Fluorescence
Scope: Genome-wide
Screen type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HeLa
Library: ThermoFisher Scientiļ¬c, siARRAY human genome siRNA library
Reagent type: siRNA
Score type: p-value
Cutoff: Complex criteria
Notes: Confidence groupings from 4 to 1 (highest level of confidence in group 4)