New insights into how the telomere shelterin protein TPP1, encoded by the ACD gene, interacts with telomerase have recently been published in Nature. In their study, researchers at the University of California, Los Angeles, have further elucidated the mechanism of telomerase activity. The telomerase enzyme complex has an essential role in cellular aging and cancer progression.

TPP1 is one of six proteins forming the shelterin complex. Shelterin functions to shield telomeres, the chromosome ends, from damage and deterioration, and TPP1 is of critical importance in recruiting and regulating telomerase. The telomerase complex acts in specific cells by adding telomeric sequence repeats, thus counteracting the shortening of telomeres happening with each round of cell division. The researchers used the method of cryo-electron microscopy, allowing them to investigate at a particularly high resolution the structured interface which the subunits of the telomerase catalytic core, TERT and TER, form with TPP1. The new knowledge about the structural basis of telomerase activity also helps to better understand known disease-associated mutations in telomerase components and might provide a basis for the development of future drugs.