Telomere Dynamics in Pluripotent Stem Cells and Cancer Cells: Implications for Cellular Aging and Oncology
Eros Lazzerini Denchi
Laboratory of genome integrity, National Cancer Institute, Bethesda, USA
invited by Prisca Berardi
Thursday 10 October 2024, at 10 am at Library of IBPC
Telomeres, the natural ends of chromosomes, resemble double-strand breaks (DSBs) and require protection by the shelterin complex to prevent aberrant activation of the DNA damage response (DDR) in somatic cells. In cancer cells, the ability to extend telomeres is a hallmark of their immortality. In this talk, I will discuss our ongoing research to define the mechanisms of telomere protection in somatic and stem cells, as well as the mechanisms of telomere elongation in cancer cells. I will focus on Alternative Lengthening of Telomeres (ALT) pathway, a recombination-based mechanism for telomere extension. To explore the genes regulating ALT activity, we developed the Telomeric ALT In situ Localization Screen (TAILS), which detects single-stranded telomeric DNA, a byproduct of ALT, at the single-cell level. By screening over 1,100 genes involved in DNA transactions, we identified novel and established modulators of the ALT pathway. Our findings reveal the critical role of histone deposition defects in ALT-associated phenotypes and highlight potential pharmacological treatments for ALT-positive cancers. This work sheds light on telomere dynamics in cancer and stem cells, offering new insights into cellular aging and oncology therapies.