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How Telomeres Solve the End-Protection Problem (HHS Only)

   
Air date: Monday, September 18, 2017, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Description: NCI Center for Cancer Research Eminent Lecture Series

Dr. de Lange's lab studies telomeres, protective elements at the ends of chromosomes critical for the stability and maintenance of the genetic information. Deficiency in telomere function can cause genomic alterations found in cancer, and the gradual loss of telomeres contributes to aging of human cells. Dr. de Lange seeks to understand how telomere protection is established and what happens when telomere function is lost during the early stages of tumor formation. Dr. de Lange’s group is working to determine the mechanism by which each shelterin protein inhibits its designated pathway, and how loss of telomere protection contributes to genome instability in human cancer. A major mechanistic insight arose from the identification of the t-loop structure of telomeres in which the single-stranded overhang is inserted in the double-stranded repeat array of the telomere, thereby hiding the telomere end from the DNA damage response. Recent data showed that the TRF2 component of shelterin is required to establish and/or maintain this structure. Since TRF2 is responsible for the repression of the ATM kinase pathway and non-homologous end joining, it is likely that the t-loop structure is critical to prevent these two pathways from acting inappropriately on chromosome ends.
Author: Titia de Lange, Ph.D., Leon Hess Professor, American Cancer Society, Porfessor Head, Laboratory of Cell Biology and Genetics, Director, Anderson Center for Cancer Research, Rockefeller University
Runtime: 1 hour