Abstract
Mammalian telomeres are composed of long arrays of TTAGGG repeats that form a nucleoprotein complex which protects the chromosome ends. Human telomere function is known to require two TTAGGG repeat factors, TRF1 and TRF2, and several interacting proteins, but the mechanism by which the DNA/protein complex prevents end to end fusion in vivo has not been elucidated. In order to better understand the role of specific telomere-associated proteins in the organisation of chromosome ends, we have studied a patient with a rare chromosome rearrangement that has given rise to an interstitial telomere. Using specific antibodies and immuno-FISH on unfixed metaphase chromosomes, we show that the proteins TRF2 and TIN2 (TIN2 interacts with TRF1) co-localise with the interstitial TTAGGG repeats. Our results demonstrate, for the first time in humans, that TRF2 and TIN2 proteins associate with interstitial duplex TTAGGG repeats, in vivo. They confirm that double stranded-telomeric repeats, even when complexed with specific proteins, are not sufficient to create a functional telomere. Finally, they suggest a possible role for proteins in stabilising interstitial TTAGGG repeats.
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Acknowledgements
The authors thank Drs E Gilson and K Ancelin (ENS, Lyon, France), Drs J Campisi and SH Kim (LBNL, Berkeley, USA) who kindly provided the antibodies. They also thank Dr E Gilson for very helpful discussion and Dr M Mitchell for reviewing the English text. They also thank the family for its participation. This work was supported by INSERM, the Association pour la Recherche contre le Cancer (ARC), and the ACI 2000 from the ministere de la Recherche.
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Mignon-Ravix, C., Depetris, D., Delobel, B. et al. A human interstitial telomere associates in vivo with specific TRF2 and TIN2 proteins. Eur J Hum Genet 10, 107–112 (2002). https://doi.org/10.1038/sj.ejhg.5200775
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DOI: https://doi.org/10.1038/sj.ejhg.5200775
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