Overview

Telomeres are specialized DNA-protein complexes that cap the ends of eukaryotic chromosomes; they are necessary for chromosomal end replication and provide chromosomal stability by protecting chromosome ends from degradation (Blackburn, 1990). As shown in Figure 1, every human chromosome end is capped with between three and 20 kb of tandemly repeated (T2AG3)n sequences, which have been shown to be evolutionarily conserved among vertebrate species (Meyne et al., 1989; Moyzis et al., 1988). The (T2AG3)n repeats comprise the part of the telomeric DNA sequence that varies in length in humans and have been implicated in aging and cancer (Holt et al., 1996).

Immediately proximal to the tandemly repeated (T2AG3)n repeats in humans are subtelomeric repeats, also called telomere associated repeats (TAR). The subtelomeric regions of human chromosomes have shared sequence homologies between different subsets of human telomeres. The subtelomeric repeat regions of human chromosomes are mosaics of shared repetitive DNA and other shared sequence homologies.

Although still relatively poorly characterized, a picture is emerging of the regions adjacent to the terminal (T2AG3)n sequences indicating a complex organization and evolutionary history (Flint et al., 1997a; Flint et al., 1997b).  Several TAR sequences have been identified and shown to cross-hybridize to different subsets of human telomeres (Brown et al., 1990; Cross et al., 1990; Flint et al., 1997a; Flint et al., 1997b; Youngman et al., 1992).

Recent sequencing data from a number of telomeric regions indicate the presence of two sub-domains in human telomeres: The regions closest to the terminal repeat contain a mosaic of very short sequences shared by many chromosomes, while the more proximal sub-domain contains longer sequences shared by fewer chromosomes (Flint et al., 1997a). The two sub-domains are separated by a block of degenerate (T2AG3)n repeats and sequences with homology to putative origins of replication. Surprisingly, this same organization of two sub-domains separated by degenerate (T2AG3)n and origins of replication is also observed in all telomeres in yeast. This amazing conservation suggests an important functional role for the organization of telomere repeats.

Unique, chromosome specific DNA for each telomere is located proximal to the subtelomeric repeats, about 100-300 kb from the end of each chromosome (National Institutes of Health et al., 1996).  This region contains the most distal unique sequence, and therefore genes, for each chromosome arm.