Fission yeast shelterin regulates DNA polymerases and Rad3(ATR) kinase to limit telomere extension.
Studies in fission yeast have previously identified evolutionarily conserved shelterin and Stn1-Ten1 complexes, and established Rad3(ATR)/Tel1(ATM)-dependent phosphorylation of the shelterin subunit Ccq1 at Thr93 as the critical post-translational modification for telomerase recruitment to telomeres. Furthermore, shelterin subunits Poz1, Rap1 and Taz1 have been identified as negative regulators of Thr93 phosphorylation and telomerase recruitment. However, it remained unclear how telomere maintenance is dynamically regulated during the cell cycle. Thus, we investigated how loss of Poz1, Rap1 and Taz1 affects cell cycle regulation of Ccq1 Thr93 phosphorylation and telomere association of telomerase (Trt1(TERT)), DNA polymerases, Replication Protein A (RPA) complex, Rad3(ATR)-Rad26(ATRIP) checkpoint kinase complex, Tel1(ATM) kinase, shelterin subunits (Tpz1, Ccq1 and Poz1) and Stn1. We further investigated how telomere shortening, caused by trt1Δ or catalytically dead Trt1-D743A, affects cell cycle-regulated telomere association of telomerase and DNA polymerases. These analyses established that fission yeast shelterin maintains telomere length homeostasis by coordinating the differential arrival of leading (Polε) and lagging (Polα) strand DNA polymerases at telomeres to modulate Rad3(ATR) association, Ccq1 Thr93 phosphorylation and telomerase recruitment.
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Ya-Ting
YT
Chang
Bettina A
BA
Moser
Toru M
TM
Nakamura
D002453:Cell Cycle / Q000235:genetics; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism*; D000089804:Shelterin Complex; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics; D059505:Telomere Homeostasis / Q000235:genetics; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000378:metabolism
C529645:Poz1 protein, S pombe; C509571:Rap1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C523518:Ten1 protein, S pombe; C104344:taz1 protein, S pombe; D064447:Checkpoint Kinase 2; C456840:rad3 protein, S pombe; D019098:Telomerase; D004259:DNA-Directed DNA Polymerase