ArticlePLoS genetics2017
Two separate pathways regulate protein stability of ATM/ATR-related protein kinases Mec1 and Tel1 in budding yeast.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- A tti1 mutation in the Tel2-Tti1-Tti2 complex specifically eliminates the cellular function of Rad3ATR, but not that of other PIKKs in fission yeast.PLoS genetics · 2026Article
- The RPA-binding domain and the KKRK motif in Rad26ATRIP cooperate at the perturbed DNA replication fork for initiating checkpoint signalling.PLoS genetics · 2026Article
- Co-translational determination of quaternary structures in chaperone factories.Nature communications · 2026Article
- FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways.Molecular cell · 2023Article
- Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens.Molecular cell · 2023Article
- TTT (Tel2-Tti1-Tti2) Complex, the Co-Chaperone of PIKKs and a Potential Target for Cancer Chemotherapy.International journal of molecular sciences · 2023Review
- Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly.American journal of human genetics · 2023Article
- The Role of Hsp90-R2TP in Macromolecular Complex Assembly and Stabilization.Biomolecules · 2022Review
- Essentiality of Sis1, a J-domain protein Hsp70 cochaperone, can be overcome by Tti1, a specialized PIKK chaperone.Molecular biology of the cell · 2022Article
- The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium.Nature communications · 2021Article
- Ddc2ATRIP promotes Mec1ATR activation at RPA-ssDNA tracts.PLoS genetics · 2019Article
- Branching the Tel2 pathway for exact fit on phosphatidylinositol 3-kinase-related kinases.Current genetics · 2018Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Checkpoint signaling requires two conserved phosphatidylinositol 3-kinase-related protein kinases (PIKKs): ATM and ATR. In budding yeast, Tel1 and Mec1 correspond to ATM and ATR, respectively. The Tel2-Tti1-Tti2 (TTT) complex connects to the Rvb1-Rvb2-Tah1-Pih1 (R2TP) complex for the protein stability of PIKKs; however, TTT-R2TP interaction only partially mediates ATM and ATR protein stabilization. How TTT controls protein stability of ATM and ATR remains to be precisely determined. Here we show that Asa1, like Tel2, plays a major role in stabilization of newly synthesized Mec1 and Tel1 proteins whereas Pih1 contributes to Mec1 and Tel1 stability at high temperatures. Although Asa1 and Pih1 both interact with Tel2, no Asa1-Pih1 interaction is detected. Pih1 is distributed in both the cytoplasm and nucleus wheres Asa1 localizes largely in the cytoplasm. Asa1 and Pih1 are required for proper DNA damage checkpoint signaling. Our findings provide a model in which two different Tel2 pathways promote protein stabilization of Mec1 and Tel1 in budding yeast.
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