Titia de Lange
The Rockefeller University
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Membership Type:
International Member
(elected 2006)
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Research Interests
The linear chromosomes of eukaryotes pose two fundamental problems. Because the universal DNA replication strategy fails to copy chromosome ends, they require a specialized duplication mechanism. The second problem originates from the DNA damage response. As the continuity of life depends on mechanisms to detect and repair lesions in DNA, cells must have the ability to distinguish their natural chromosome ends from sites of DNA damage. The ends of eukaryotic chromosomes carry specific elements, telomeres, that mediate both the replication and protection of the terminal DNA. My goal is to understand how telomeres work. Our biochemical and cell biological studies on mammalian cells have identified a protein complex, shelterin, that binds telomeres but not other DNA ends. We found that shelterin is required for the normal duplication of chromosome ends and also protects the ends from the DNA damage response. Collaborative work with Dr. Jack Griffith (UNC, Chapel Hill) has revealed that telomeres form a higher order structure (the t-loop) in which the chromosome end is sequestered. We have proposed that t-loops represent an architectural solution to several of the problems of chromosome ends. Insights into the basic biology of telomeres have medical relevance since telomere dysfunction is implicated in aging and cancer.
