11 The Structural Biology of Telomeres

Abstract

Although the last 10 years have witnessed an explosion in telomere biology with the identification of a large number of protein components of yeast and human telomeres, structural information on telomeres and their subcomplexes is in its infancy. Despite this, the three-dimensional structural information that has been obtained provides important and detailed insights into the function and evolutionary relationship of telomeric proteins. The first three-dimensional structure of a telomeric protein was determined in 1996—the DNA-binding domain of Saccharomyces cerevisiae Rap1p in complex with its double-stranded telomeric DNA-binding site (Konig et al. 1996). This was followed in 1998 by the structure of the Oxytricha nova telomere end-binding protein (TEBPα-β) heterodimer in complex with the single-stranded G-overhang (Horvath et al. 1998). Since then, a number of other structures of telomeric proteins and their complexes have been determined. This chapter summarizes the three-dimensional structural information on telomeric DNA and telomeric protein/DNA complexes obtained from direct structural methods such as X-ray crystallography and nuclear magnetic resonance (NMR). Features of the overall architecture of telomeres that have emerged from biological and biochemical studies in combination with electron microscopy are also highlighted.

DNA G-QUADRUPLEX STRUCTURES
The sequence conservation of telomeric DNA repeats, organized in a region of double-stranded DNA and a single-stranded G-overhang, not only imparts on the DNA the ability to recruit telomere-binding proteins, but also gives telomeric DNA unusual properties. The composition of telomeric DNA repeats containing runs of three or four guanines imparts on the single-stranded G-overhang the inherent ability to form...