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Originally published as MBC in Press, 10.1091/mbc.E05-09-0904 on November 30, 2005

Vol. 17, Issue 2, 944-954, February 2006

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Cell Cycle-dependent Recruitment of Telomerase RNA and Cajal Bodies to Human Telomeres

Beáta E. Jády *, Patricia Richard *, Edouard Bertrand {dagger}, and Tamás Kiss * {ddagger}

* Laboratoire de Biologie Moléculaire Eucaryote du CNRS, UMR5099, IFR109, 31062 Toulouse, France; {dagger} Institut de Génétique Moléculaire, 34000 Montpellier, France; and {ddagger} Biological Research Center, Hungarian Academy of Sciences, H-6701 Szeged, Hungary

Submitted September 30, 2005; Revised November 4, 2005; Accepted November 17, 2005
Monitoring Editor: Marvin P. Wickens

Telomerase is a ribonucleoprotein enzyme that counteracts replicative telomere erosion by adding telomeric sequence repeats onto chromosome ends. Despite its well-established role in telomere synthesis, telomerase has not yet been detected at telomeres. The RNA component of human telomerase (hTR) resides in the nucleoplasmic Cajal bodies (CBs) of interphase cancer cells. Here, in situ hybridization demonstrates that in human HeLa and Hep2 S phase cells, besides accumulating in CBs, hTR specifically concentrates at a few telomeres that also accumulate the TRF1 and TRF2 telomere marker proteins. Surprisingly, telomeres accumulating hTR exhibit a great accessibility for in situ oligonucleotide hybridization without chromatin denaturation, suggesting that they represent a structurally distinct, minor subset of HeLa telomeres. Moreover, we demonstrate that more than 25% of telomeres accumulating hTR colocalize with CBs. Time-lapse fluorescence microscopy demonstrates that CBs moving in the nucleoplasm of S phase cells transiently associate for 10-40 min with telomeres. Our data raise the intriguing possibility that CBs may deliver hTR to telomeres and/or may function in other aspects of telomere maintenance.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-09-0904) on November 30, 2005.

Abbreviations used: CB, Cajal body; hTR, human telomerase RNA; hTERT, human telomerase reverse transcriptase.

Address correspondence to: Tamás Kiss (tamas{at}ibcg.biotoul.fr).




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