I began my research career investigating the cellular responses to damaged telomeres, telomeres being DNA and protein complexes that protect the ends of chromosomes in eukaryotic cells. During my PhD, I was able to generate yeast cells proliferating without telomeres, under certain conditions. The existence of cells with linear chromosomes lacking telomeres and the fact that they proliferate well over months and years was very surprising, because it has been thought, based on experimental data, that telomeres were essential for the viability and proliferation of cells, from yeast to man.
One possibility was telomeres were being replaced by other, unknown DNA structures. I found this was not the case. Instead, cells without telomeres continuously re-shaped their genomes, mostly through deletions and amplifications of chromosome regions. This loss and amplification of chromosome regions is also characteristic of many cancer cells and is associated with inactivation of tumour suppressors and activation of oncogenes.
Another possibility to explain how cells proliferate without telomeres is that special proteins bind chromosome ends and protect them. This hypothesis is supported by the identification of a protein that has little impact on the wellbeing of normal cells, however it becomes essential for survival in the absence of telomeres.
A model system of cells without telomeres would be ideal to identify and characterize factors, including genes, that influence the process of chromosomal instability. Once identified and understood in yeast, we will address their role in mammalian tissue culture.
Telomeres in ageing and cancer for MRES students