A highly conserved repetitive DNA sequence, (TTAGGG)., has been isolated from a human recombinant repetitive DNA library. Quantitative hybridization to chromosomes sorted by flow cytometry indicates that comparable amounts of this sequence are present on each human chromosome. Both fluorescent in situ hybridization and BAL-31 nuclease digestion experiments reveal major clusters of this sequence at the telomeres of all human chromosomes. The evolutionary conservation of this DNA sequence, its terminal chromosomal location in a variety of higher eukaryotes (regardless of chromosome number or chromosome length), and its similarity to functional telomeres isolated from lower eukaryotes suggest that this sequence is a functional human telomere.The human genome contains a variety of DNA sequences present in multiple copies (1). These repetitive DNA sequences are thought to arise by many mechanisms, from direct sequence amplification by the unequal recombination of homologous DNA regions to the reverse flow of genetic information (2). While it is likely that some ofthese repetitive DNA sequences influence the structure and function of the human genome, little experimental evidence supports this idea at present. We reasoned, however, that evolutionary conservation of a particular repetitive DNA sequence family might imply that the sequence is essential to cellular function. To isolate highly conserved repetitive DNA sequences, we constructed a recombinant human repetitive DNA library (pHuR library, for plasmid human repeat) and isolated clones that shared a high degree of sequence identity with rodent repetitive DNA. Four of the six most conserved cloned sequences isolated in this manner consisted of tandem arrays of the alternating (dG-dT)-(dA-dC) sequence, known to be ubiquitously interspersed in eukaryotic genomes and capable of forming the alternative Z-DNA conformation (3).The remaining two highly conserved cloned DNA sequences consisted of tandem arrays of the hexanucleotide sequence (TTAGGG), ¶ identical to the hexanucleotide sequence known to be at the telomeres of trypanosome chromosomes (4, 5). A telomere is functionally defined as a region of DNA at the molecular end of a linear chromosome that is required for replication and stability of the chromosome (6). Replicating a linear DNA molecule presents unique challenges, since all known DNA polymerases require a polynucleotide primer bearing a 3'-hydroxyl group. A variety of mechanisms are used to circumvent this replication problem, from the production of concatemeric genomes (7) to the evolution of specific telomere terminal transferase enzymes (8). In addition to their role in chromosome replication, functional telomeric DNA sequences are believed to confer stability to chromosomes, preventing the end-to-end fusions and DNA degradation normally observed after breakage of chromosomes by x-irradiation or physical rupture (6).In this paper, we present the results of fluorescent in situ hybridization (9) and BAL-31 nuclease digestion experiments (4, 5), ...

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