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At the end of the millennium, a view of the end

Nature Genetics volume 23, pages 382–383 (1999)Cite this article

The ends of human chromosomes, telomeres, contain long stretches of a tandemly arranged hexameric sequence, TTAGGG, that is bound by specific proteins1. In normal human cells, telomeres progressively shorten with each successive cell division2, ultimately leading to growth arrest. In tumour cells, this decline is halted by activation of telomerase3, a reverse transcriptase that extends the telomeric TTAGGG repeat4. Telomere length in nearly all tumour cells is stably maintained, suggesting that regulatory mechanisms limit telomere elongation by telomerase. But what is the molecular nature of the mechanism that governs telomere length? To address this question, two overlapping strategies are being pursued: identification and functional characterization of (i) the proteins that localize to the telomere, and (ii) those that associate with the telomerase holoenzyme complex. On page 405 of this issue, Judith Campisi and colleagues5 advance the former strategy in describing a new protein that regulates telomere length in human cells by interacting with the human telomeric-repeat binding factor 1 (TRF1).

The revelation6 that the telomere loops back on itself, forming a large 'DNA lariat' or telomere duplex loop (t-loop) structure, has effected a paradigm shift in our view of the mammalian telomere terminus (see figure). It is believed that the long 3′ G-rich single-stranded overhang of mammalian cells invades the double-stranded telomeric repeats, creating a single-stranded displacement loop6 (d-loop) and masking telomere termini.

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  1. Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, 75390, Texas, USA

    Jerry W Shay

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  1. Jerry W Shay
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Shay, J. At the end of the millennium, a view of the end. Nat Genet 23, 382–383 (1999). https://doi.org/10.1038/70480

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