NTU discovers how cell stabilizes its division through terminating telomere replication, inspires cancer research Glossary : Telomere a region of sequences protecting the end of the chromosome and stabilizing cells Telomerase synthesizes telomeres CDKs, Aurora and Polo-like kinases major regulatory molecules coordinating cell division Phosphorylation a metabolic process in the cell cycle, triggering the action of telomeres Protein phosphatase 2A (PP2A) a special protein in the de-phosphorylation process The research team of NTU, which is led by Prof. Shu-Chun Teng from the Department of Microbiology, College of Medicine, has discovered the mechanism related to DNA replication and the stability of cells. This discovery is very likely to have crucial implications for cancer research and treatment, as understanding this mechanism might allow scientists to prevent harmful chromosome rearrangements and genomic instability of cancer. This research has been accepted and published by the reputational journal Nature Communications in 2014. Teng’s team specializes in studying the function of ‘telomere’ – a region of sequences protecting the end of the chromosome and stabilizing cells. The quest of how cells synthesize telomeres has long been a puzzle for biologists. Nevertheless, the answer to it might help biologists understand why most cells stay still while cancer cells actively execute cell division. Drawn from previous studies in the field, it is known that there are three major regulatory molecules- CDKs, Aurora and Polo-like kinases- coordinating cell division. In this coordination, Cdc13- one of the CDK’s substracts- plays a decisive role in the telomere protection in live organisms. In addition, recent reports have suggested that ‘phosphorylation’ – a metabolic process in the cell cycle – may trigger the action of telomere. However, this suggestion lacks empirical justification. Therefore, Teng’s team aims at addressing this research gap by investigating the effects of Cdc13 phosphorylation. Through the experiment on yeast, Teng’s team discovers how important telomeres are in stabilizing cells during the DNA replication process. In their experiment, they inactivated the two regulatory molecules, Cdc13 and Aurora kinase, and found that this inactivation causes elongated telomeres and prolonged cell division phase. Besides, they also found a special protein: ‘protein phosphatase 2A (PP2A)’, in the de-phosphorylation process of Cdc13 substrates. It promotes telomerase departure in the telomeres while opposing Cdc13’s activation. In other words, phosphatase and Aurora kinase use distinct mechanisms to release telomerase from telomeres; they act independently but complimentarily. Teng’s team answers the puzzle for the biologists around the world, and reveals the mechanism of how telomeres function in the cell cycle and stabilize cells. It is interesting that cells use multiple pathways to release telomerase. Teng’s team discovers that not only the initiation but also the termination of telomerase recruitment plays an important role in telomere maintenance and cell cycle progression. Teng’s team further predicts that in a single cell, PP2A phosphatase might facilitate the telomerase release on some telomeres, whereas Aurora kinase might promotes telomerase release on other telomeres. Their prediction hints the direction of future research. (Insert Figure 7: PP2A phosphatase and Aurora kinase promoted telomerase departure.) Reference Zih-Jie Shen, Pang-Hung Hsu, Yu- Tai Su, Chia-Wei Yang, Li Kao, Shun-Fu Tseng, Ming-Daw Tsai & Shu-Chun Teng. PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase. Nat. Commun. 5:5312 DOI:10.1038/ ncomms6312 (2014). Professor Shu-Chun Teng Department of Microbiology shuchunteng@ntu.edu.tw