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- Title
Tel1<sup>ATM</sup> and Rad3<sup>ATR</sup> kinases promote Ccq1-Est1 interaction to maintain telomeres in fission yeast.
- Authors
Moser, Bettina A; Chang, Ya-Ting; Kosti, Jorgena; Nakamura, Toru M
- Abstract
The evolutionarily conserved shelterin complex has been shown to play both positive and negative roles in telomerase regulation in mammals and fission yeast. Although shelterin prevents the checkpoint kinases ATM and ATR from fully activating DNA damage responses at telomeres in mammalian cells, those kinases also promote telomere maintenance. In fission yeast, cells lacking both Tel1 (ATM ortholog) and Rad3 (ATR ortholog) fail to recruit telomerase to telomeres and survive by circularizing chromosomes. However, the critical telomere substrate(s) of Tel1ATM and Rad3ATR was unknown. Here we show that phosphorylation of the shelterin subunit Ccq1 on Thr93, redundantly mediated by Tel1ATM and/or Rad3ATR, is essential for telomerase association with telomeres. In addition, we show that the telomerase subunit Est1 interacts directly with the phosphorylated Thr93 of Ccq1 to ensure telomere maintenance. The shelterin subunits Taz1, Rap1 and Poz1 (previously established inhibitors of telomerase) were also found to negatively regulate Ccq1 phosphorylation. These findings establish Tel1ATM/Rad3ATR-dependent Ccq1 Thr93 phosphorylation as a critical regulator of telomere maintenance in fission yeast.
- Subjects
MOLECULAR biology; DNA polymerases; LEAVENING agents; CHEMICAL reactions; DNA damage; BIOCHEMICAL genetics; CELL nuclei
- Publication
Nature Structural & Molecular Biology, 2011, Vol 18, Issue 12, p1408
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb.2187