Tpz1-Ccq1 and Tpz1-Poz1 Interactions within Fission Yeast Shelterin Modulate Ccq1 Thr93 Phosphorylation and Telomerase Recruitment

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Proper maintenance of telomeres is essential for maintaining genomic stability, and genomic instability caused by dysfunctional telomeres could lead to accumulation of mutations that may drive tumor formation. Telomere dysfunction has also been linked to premature aging caused by depletion of stem cells. Therefore, it is important to understand how cells ensure proper maintenance of telomeres. Mammalian cells and fission yeast cells utilize an evolutionarily conserved multi-subunit telomere protection complex called shelterin to ensure protection against telomere fusions by DNA repair factors and cell cycle arrest by DNA damage checkpoint kinases. However, previous studies have not yet fully established how protein-protein interactions within the shelterin complex contribute to the regulation of DNA damage checkpoint signaling and telomerase recruitment. By utilizing separation of function mutations that specifically disrupt either Tpz1-Ccq1 or Tpz1-Poz1 interaction within the fission yeast shelterin, we establish that Tpz1-Ccq1 interaction is essential for phosphorylation of Ccq1 by the DNA damage checkpoint kinases Rad3ATR and Tel1ATM that is needed for telomerase recruitment to telomeres, while Tpz1-Poz1 interaction prevents Ccq1 phosphorylation by promoting Poz1 association with telomeres. These findings thus establish for the first time how protein-protein interactions within the shelterin complex modulate checkpoint kinase-dependent phosphorylation essential for telomerase recruitment.

Vyšlo v časopise: Tpz1-Ccq1 and Tpz1-Poz1 Interactions within Fission Yeast Shelterin Modulate Ccq1 Thr93 Phosphorylation and Telomerase Recruitment. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004708
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004708

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