13 Mammalian Telomeres

Abstract

As in most other eukaryotes, the ends of mammalian chromosomes are protected by the combined action of telomeric DNA, telomere-associated proteins, and telomerase. In the decade since the last Cold Spring Harbor Laboratory Telomere Monograph was published, substantial progress has been made on each aspect of mammalian telomere biology. Important facets of the DNA component, including the t-loop configuration and the structure of the telomere terminus, have been illuminated; a telomere-specific protein complex, now referred to as shelterin, has been identified; and several DNA-damage response and repair factors have been implicated in telomere function. Studies of telomere pathology, resulting from shelterin inhibition or other insults, have revealed the fate of dysfunctional telomeres and their impact on chromosomes and cells. Furthermore, the principles of telomere length homeostasis and the role of shelterin in controlling telomere elongation by telomerase have emerged. This chapter focuses on the DNA and protein components of mammalian telomeres and the mechanisms of telomere function. The details of mammalian telomerases are discussed in Chapters 2 and 3 and aspects of telomere function that relate to cancer and aging are covered in Chapters 4–6.

TELOMERIC DNA
The Telomeric TTAGGG Repeat Array
Mammals and all other vertebrates have telomeres made up of tandem TTAGGG repeats (Fig. 1) (Moyzis et al. 1988; Meyne et al. 1989). This sequence is dictated by telomerase and may be the oldest telomeric repeat sequence because it is also found in several fungi, protozoa, and plants. The length of the TTAGGG repeat tract is an...