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

A synthetic lethal screen identifies ATR-inhibition as a novel therapeutic approach for POLD1-deficient cancers.

Hocke S, Guo Y, Job A, Orth M, Ziesch A, Lauber K, De Toni EN, Gress TM, Herbst A, Goeke B, Gallmeier E

The phosphoinositide 3-kinase-related kinase ATR represents a central checkpoint regulator and mediator of DNA-repair. Its inhibition selectively eliminates certain subsets of cancer cells in various tumor types, but the underlying genetic determinants remain enigmatic. Here, we applied a synthetic lethal screen directed against 288 DNA-repair genes using the well-defined ATR knock-in model of DLD1 colorectal cancer cells to identify potential ... [more]

Oncotarget Feb. 09, 2016; 7(6);7080-95 [Pubmed: 26755646]

Throughput

  • Low Throughput

Related interactions

InteractionExperimental Evidence CodeDatasetThroughputScoreCurated ByNotes
XRCC5 ATR
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
-
XRCC5 ATR
Reconstituted Complex
Reconstituted Complex

An interaction is inferred between proteins in vitro. This can include proteins in recombinant form or proteins isolated directly from cells with recombinant or purified bait. For example, GST pull-down assays where a GST-tagged protein is first isolated and then used to fish interactors from cell lysates are considered reconstituted complexes (e.g. PUBMED: 14657240, Fig. 4A or PUBMED: 14761940, Fig. 5). This can also include gel-shifts, surface plasmon resonance, isothermal titration calorimetry (ITC) and bio-layer interferometry (BLI) experiments. The bait-hit directionality may not be clear for 2 interacting proteins. In these cases the directionality is up to the discretion of the curator.

Low-BioGRID
-

Curated By

  • BioGRID