4 Telomere Proteins

Abstract

Telomeres are the DNA protein complexes found at the ends of linear chromosomes. When the first telomeric DNA sequence was determined (Blackburn and Gall 1978), attention became focused on the DNA component of telomeres. This was a fruitful approach, leading to the discovery of the telomere-replicating enzyme, telomerase (see Greider; Blackburn, both this volume). However, the functions of telomeres cannot be understood from their DNA sequence alone. Knowledge of their protein components is also required.

Telomere proteins comprise a class of structural proteins that bind sequence-specifically to telomeric DNA (Fig. 1). Telomere proteins cap the ends of chromosomes, preventing nucleolytic degradation and end-to-end ligation, and thus confer stability to chromosomes. They are involved in chromosome localization, in nuclear architecture, and in repression of the expression of adjacent genes. Telomere proteins presumably also affect the accessibility of telomeric DNA to telomerase. In this chapter, we review the structure and function of these trans-acting protein factors: how they interact with telomeric DNA, how they interact with other proteins and with nuclear structures, and how they mediate telomere functions.

Telomeric DNA usually consists of tandemly repeated sequences with one strand rich in guanosine (see Henderson, this volume). The G-rich strand is always oriented in the 5′ to 3′ direction toward the end of the chromosome. For example, human telomeres have a T₂AG₃ repeat sequence, Oxytricha telomeres have T₄G₄ repeats, Tetrahymena has T₂G₄ repeats, and Saccharomyces has a more irregular sequence of Ts and Gs that can be approximated by TG_1–3 Telomeric...