Synthetic Lethality

A genetic interaction is inferred when mutations or deletions in separate genes, each of which alone causes a minimal phenotype, result in lethality when combined in the same cell under a given condition.

Publication

Genome-Wide CRISPR-Cas9 Screen Reveals Selective Vulnerability of ATRX-Mutant Cancers to WEE1 Inhibition.

Liang J, Zhao H, Diplas BH, Liu S, Liu J, Wang D, Lu Y, Zhu Q, Wu J, Wang W, Yan H, Zeng YX, Wang X, Jiao Y

The tumor suppressor gene ATRX is frequently mutated in a variety of tumors including gliomas and liver cancers, which are highly unresponsive to current therapies. Here, we performed a genome-wide synthetic lethal screen, using CRISPR-Cas9 genome editing, to identify potential therapeutic targets specific for ATRX-mutated cancers. In isogenic hepatocellular carcinoma (HCC) cell lines engineered for ATRX loss, we identified 58 ... [more]

Cancer Res. Dec. 01, 2019; 80(3);510-523 [Pubmed: 31551363]

Throughput

  • Low Throughput

Ontology Terms

  • phenotype: growth abnormality (HP:0001507) [viability (PATO:0000169)]

Additional Notes

  • CRISPR GI screen
  • Cell Line: PLC-PRF-5 (Hepatoma Cell Line)
  • Experimental Setup: Timecourse
  • GIST: A-phenotypic negative genetic interaction
  • Library: GeckoV2
  • Significance Threshold: Authors looked for genes which We then searched for genes targeted by the sgRNAs that were represented at nearly the same level at T0 as at T21 in ATRX WT cells, but depleted in ATRX KO cells at T21 compared with T0. Under these stringent criteria, we identified 58 genes, which were essential for viability in ATRX KO cells but nonessential for ATRX WT cells, as potential synthetic lethal partners for ATRX and signified genes that met this criteria in a hit list in the supp file

Related interactions

InteractionExperimental Evidence CodeDatasetThroughputScoreCurated ByNotes
ATRX SMC1A
Affinity Capture-Western
Affinity Capture-Western

An interaction is inferred when a bait protein is affinity captured from cell extracts by either polyclonal antibody or epitope tag and the associated interaction partner identified by Western blot with a specific polyclonal antibody or second epitope tag. This category is also used if an interacting protein is visualized directly by dye stain or radioactivity. Note that this differs from any co-purification experiment involving affinity capture in that the co-purification experiment involves at least one extra purification step to get rid of potential contaminating proteins.

Low-BioGRID
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Curated By

  • BioGRID