51. PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase.
- Author
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Shen ZJ, Hsu PH, Su YT, Yang CW, Kao L, Tseng SF, Tsai MD, and Teng SC
- Subjects
- Aurora Kinases metabolism, Protein Phosphatase 2 metabolism, Saccharomyces cerevisiae Proteins metabolism, Telomerase metabolism, Telomere metabolism, Telomere-Binding Proteins metabolism, Aurora Kinases physiology, Cell Division physiology, G2 Phase physiology, Protein Phosphatase 2 physiology, Saccharomyces cerevisiae Proteins physiology, Telomerase physiology, Telomere physiology, Telomere-Binding Proteins physiology
- Abstract
In yeast, the initiation of telomere replication at the late S phase involves in combined actions of kinases on Cdc13, the telomere binding protein. Cdc13 recruits telomerase to telomeres through its interaction with Est1, a component of telomerase. However, how cells terminate the function of telomerase at G2/M is still elusive. Here we show that the protein phosphatase 2A (PP2A) subunit Pph22 and the yeast Aurora kinase homologue Ipl1 coordinately inhibit telomerase at G2/M by dephosphorylating and phosphorylating the telomerase recruitment domain of Cdc13, respectively. While Pph22 removes Tel1/Mec1-mediated Cdc13 phosphorylation to reduce Cdc13-Est1 interaction, Ipl1-dependent Cdc13 phosphorylation elicits dissociation of Est1-TLC1, the template RNA component of telomerase. Failure of these regulations prevents telomerase from departing telomeres, causing perturbed telomere lengthening and prolonged M phase. Together our results demonstrate that differential and additive actions of PP2A and Aurora on Cdc13 limit telomerase action by removing active telomerase from telomeres at G2/M phase.
- Published
- 2014
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