Cancer progression and organismal ageing are complex biological processes that share common molecular mechanisms. Although the exact nature of their relationship is currently unclear, telomere biology has emerged as a key link between these two processes.
Group Leader of the Laboratory of Telomeres and Genome Integrity
Telomeres, telomerase, DNA replication, DNA recombination, DNA damage, yeast
Telomeres, the physical ends of eukaryotic chromosomes, help distinguish natural chromosome ends from DNA breaks in need of repair. Dysfunctional telomeres result in DNA damage checkpoint activation and cell cycle arrest. Telomeres progressively shorten due to incomplete DNA replication and nucleolytic degradation. When telomeres are critically shortened, cells can no longer divide, reaching a state known as replicative senescence. Shortening is counteracted by telomerase, the specialized reverse transcriptase that elongates telomeres. However, most human somatic cells do not express sufficient telomerase to prevent telomere shortening, which has been proposed as one reason why human individuals age.
Replicative senescence functions as a barrier to tumorigenesis since cancer cells need to maintain their telomeres to continue proliferating. Most cancer cells overcome this barrier via the activation of telomerase. However, ~15% of human cancers use telomerase-independent mechanisms termed Alternative Lengthening of Telomeres (ALT). The goal of Michael Chang’s lab is to understand the process of senescence and to characterize how cells maintain their telomeres, both by telomerase and telomerase-independent mechanisms.