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

Titia de Lange, PhD

Leon Hess Professor
Laboratory of Cell Biology and Genetics

The Rockefeller University

New York, New York

Dr de Lange's Website

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.