PhD Student Seminar

Department of Life Sciences

Control of telomere length by the human telomeric protein TRF1

 

Bas van Steensel, Titia de Lange, Nature 385, 740-43 (1997)

speaker: ¥ø³Õ­× (d848206)


Abstract

The terminus of a DNA helix has been called its Achilles* heel. Thus to prevent possible incomplete replication and instability of the termini of liner DNA, eukaryotic chromosomes end in characteristic repetive DNA sequences within specialized structures called telomerase. In immortal cells, loss of telomeric DNA due to degradation or incomplete replication is apparently balanced by telomere elongation, which may involve de novo synthesis of additional repeats by a novel DNA polymerase called telomerase.

Several telomere-related proteins such as Rap1 and Taz1 have been cloned. Another major protein component of human telomeres, also has been identified. This factor , TRF1 contains one Myb-type DNA binding repeat and an acidic domain which is involved in telomere length control. In this issue, overexpression of TRF in the telomerase-positive tumour-cell line HT1080 resulted in a gradual and progressive telomere shortening. Conversely, telomere enongation was induced by expression of a dominant-negative feedback mechanism that stabilizes telomere length.

And the TRF1 does not detectably affect the expression of telomerase, we propose that the binding of TRF1 controls telomere length in cis by inhibiting the action of telomerase at the ends of individual telomeres.


References

1. Harley, C. B., Futcher, A. B. & Greider, C. W. Telomeres shorten during

ageing of human fibroblasts. Nature 345, 458-460 (1990)

2. Chong, L. et al. A human telomeric protein. Science 270, 1663-1667 (1995)

3. Marcia B. Cells Count Proteins to Keep Their Telomeres in Line. Science

275, 928 (1997)

4. David S. Differentmeans to common ends. Nature 385, 676 (1997)