The team, led by Hao Wu, Ph.D., an associate professor in the Department of Biochemistry and Molecular Biology at MD Anderson, published their findings in the journal Nature Communications. Telomerase is a complex enzyme made up of multiple subunits, including the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC).
In healthy cells, telomerase activity is tightly regulated to ensure that telomeres are maintained at an appropriate length. However, in cancer cells, telomerase activity is often upregulated, allowing the cells to bypass cell death and continue dividing indefinitely.
Understanding the self-assembly process of telomerase is critical for developing new therapeutic strategies to inhibit telomerase activity in cancer cells. In this study, the researchers used a combination of biochemical, biophysical, and structural biology techniques to dissect the individual steps involved in the assembly of telomerase. They found that the TERT protein first forms a dimer, which then binds to TERC to form a stable complex.
Additional components are recruited to the complex in a stepwise manner, ultimately leading to the formation of a fully assembled and functional telomerase holoenzyme. The researchers also identified key molecular interactions that are essential for the assembly process. These findings provide new insights into the regulation of telomerase activity and offer potential targets for the development of telomerase inhibitors.
"By understanding how telomerase assembles, we can identify potential points of intervention to disrupt the enzyme activity and exploit its vulnerability in cancer cells," said Dr. Wu. "Targeting telomerase assembly could be a promising therapeutic strategy for a wide range of cancers."
The study highlights the importance of basic research in understanding the fundamental mechanisms of cellular processes, which can pave the way for the development of novel cancer treatments.
