How telomeres solve the end-protection problem
Titia de Lange, Ph.D.
Leon Hess Professor
American Cancer Society Professor
Head, Laboratory of Cell Biology and Genetics
Director, Anderson Center for Cancer Research
The Rockefeller University
Dr. de Lange studied biochemistry at the University of Amsterdam and the Netherlands Cancer Institute. As part of her undergraduate training, she worked on globin gene expression at the National Institute for Medical Research (Mill Hill, London). She did her graduate work on the activation and transcription of surface antigen genes in typanosomes. After obtaining her Ph.D. in 1985, she was a postdoctoral fellow with Harold Varmus at the University of California, San Francisco, where she was one of the first to isolate the telomeres of human chromosomes.
Titia de Lange’s group is now 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.
This page was last updated on Wednesday, August 11, 2021