Abstract: Series 105, Lecture 4
The Harvey Lectures Series 105 (2009—2010)
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Lecture #4: Thursday, February 18, 2010 — Time and Location
How Telomeres Solve the End-Protection Problem
Titia de Lange, PhD
Leon Hess Professor
Laboratory of Cell Biology and Genetics
The Rockefeller University
New York, New York
For reasons that are unclear, eukaryotes evolved linear chromosomes, despite the problems associated with chromosome ends. Telomerase solves the ‘end-replication problem’, which refers to the inability of the canonical DNA replication machinery to duplicate the ends of linear DNA. Our work focuses on the ‘end-protection problem’: the requirement for chromosome ends to remain protected from the DNA damage response pathways that can detect and repair broken chromosomes. Most of the basic principles of how mammalian telomeres solve the end-protection problem have now been established. The key factor in this process is shelterin, a six-subunit telomeric protein complex that prevents activation of the ATM- and ATR kinases and blocks the two main double-strand break repair pathways, NHEJ and HDR.