Gene interactions and pathways from curated databases and text-mining
Genes Dev 2010, PMID: 20810650

A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability.

Hurov, Kristen E; Cotta-Ramusino, Cecilia; Elledge, Stephen J

In response to DNA damage, cells activate a complex signal transduction network called the DNA damage response (DDR). To enhance our current understanding of the DDR network, we performed a genome-wide RNAi screen to identify genes required for resistance to ionizing radiation (IR). Along with a number of known DDR genes, we discovered a large set of novel genes whose depletion leads to cellular sensitivity to IR. Here we describe TTI1 (Tel two-interacting protein 1) and TTI2 as highly conserved regulators of the DDR in mammals. TTI1 and TTI2 protect cells from spontaneous DNA damage, and are required for the establishment of the intra-S and G2/M checkpoints. TTI1 and TTI2 exist in multiple complexes, including a 2-MDa complex with TEL2 (telomere maintenance 2), called the Triple T complex, and phosphoinositide-3-kinase-related protein kinases (PIKKs) such as ataxia telangiectasia-mutated (ATM). The components of the TTT complex are mutually dependent on each other, and act as critical regulators of PIKK abundance and checkpoint signaling.

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Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • IRef Intact Interaction: TTI1 — TELO2 (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: TTI1 — TELO2 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: TTI1 — ATR (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: TTI1 — ATM (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: TTI1 — ATM (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of TELO2-TTI1-TTI2-TTI2-TTI1-TELO2-TTI2-TTI1-TELO2 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of ATM-TTI1-MTOR-ATR-PRKDC-SMG1 (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of ATM-TTI1-TTI2-ATM-TTI2-TTI1 (association, anti bait coimmunoprecipitation)
In total, 19 gene pairs are associated to this article in curated databases