Telomerase (green) escapes the nucleoli (red) in cancer cells (bottom).


Telomerase helps cancerous cells survive by extending telomeres at the end of chromosomes. According to new results from Judy Wong, Leonard Kusdra, and Kathleen Collins (University of California, Berkeley, CA), cancer cells recruit additional telomerase by setting it free from its subnuclear storage depot.

Telomerase is activated upon association of two subunits, telomerase reverse transcriptase (TERT) and telomerase RNA, into a ribonucleoprotein (RNP) complex. Collins' group tracked the active form in normal and cancerous cells by expressing GFP-labeled TERT in limiting amounts that would assemble rapidly with the RNP. This technique revealed that telomerase differed mainly in its location. “A normal cell hides telomerase, by tying it to the nucleolus,” says Collins. In these cells, telomerase was concentrated in the nucleoplasm during S phase, when its activity is required to maintain chromosome ends. In contrast, transformed cells released all of their telomerase from the nucleoli, regardless of cell cycle phase.

The proteins that control telomerase localization are not yet known, but the ability of transformed cells to bypass this regulation may give them a twofold advantage. First, telomerase would be more effective on an established telomere because more of it is released from nucleolar stores. Additionally, continuous release of telomerase may support the high genomic instability of cancerous cells: adding telomeres to broken chromosome ends might allow normal segregation of rearranged chromosomes that might otherwise arrest the cell cycle. ▪


Wong, J.M.Y., et al.
Nat. Cell Biol.