DOI: 10.1126/science.1138596. Protein Composition of Catalytically Active Human Telomerase from Immortal Cells

Protein Composition of Catalytically Active Human Telomerase from Immortal Cells

10.1126/science.1138596

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Telomerase is a ribonucleoprotein enzyme complex that adds 5′-TTAGGG-3′ repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for ∼90% of human cancers. We have purified human telomerase ∼10 8 -fold, with the final elution dependent on the enzyme's ability to catalyze nucleotide addition onto a DNA oligonucleotide of telomeric sequence, thereby providing specificity for catalytically active telomerase. Mass spectrometric sequencing of the protein components and molecular size determination indicated an enzyme composition of two molecules each of telomerase reverse transcriptase, telomerase RNA, and dyskerin.

Bibliography

Cohen, S. B., Graham, M. E., Lovrecz, G. O., Bache, N., Robinson, P. J., & Reddel, R. R. (2007). Protein Composition of Catalytically Active Human Telomerase from Immortal Cells. Science, 315(5820), 1850â1853.

Authors 6

Scott B. Cohen (first)
Mark E. Graham (additional)
George O. Lovrecz (additional)
Nicolai Bache (additional)
Phillip J. Robinson (additional)
Roger R. Reddel (additional)

References 22 Referenced 540

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C. B. Harley, A. B. Futcher, C. W. Greider, Nature345, 458 (1990). (10.1038/345458a0) / Nature (1990)
A. M. Olovnikov, J. Theor. Biol.41, 181 (1973). (10.1016/0022-5193(73)90198-7) / J. Theor. Biol. (1973)
C. W. Greider, E. H. Blackburn, Cell43, 405 (1985). (10.1016/0092-8674(85)90170-9) / Cell (1985)
10.1126/science.276.5312.561
10.1126/science.277.5328.955
10.1126/science.7544491
J. Lingner, T. R. Cech, Proc. Natl. Acad. Sci. U.S.A.93, 10712 (1996). (10.1073/pnas.93.20.10712) / Proc. Natl. Acad. Sci. U.S.A. (1996)
C. Wenz et al., EMBO J.20, 3526 (2001). (10.1093/emboj/20.13.3526) / EMBO J. (2001)
G. Schnapp, H. Rodi, W. J. Rettig, A. Schnapp, K. Damm, Nucleic Acids Res.26, 3311 (1998). (10.1093/nar/26.13.3311) / Nucleic Acids Res. (1998)
Materials and methods are available as supporting material on Science Online.
G. Wallweber, S. Gryaznov, K. Pongracz, R. Pruzan, Biochemistry42, 589 (2003). (10.1021/bi026914a) / Biochemistry (2003)
T. M. Bryan, A. Englezou, M. A. Dunham, R. R. Reddel, Exp. Cell Res.239, 370 (1998). (10.1006/excr.1997.3907) / Exp. Cell Res. (1998)
N. S. Heiss et al., Nat. Genet.19, 32 (1998). (10.1038/ng0598-32) / Nat. Genet. (1998)
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J. R. Mitchell, E. Wood, K. Collins, Nature402, 551 (1999). (10.1038/990141) / Nature (1999)
M. Armanios et al., Proc. Natl. Acad. Sci. U.S.A.102, 15960 (2005). (10.1073/pnas.0508124102) / Proc. Natl. Acad. Sci. U.S.A. (2005)
T. Vulliamy et al., Nature413, 432 (2001). (10.1038/35096585) / Nature (2001)
T. L. Beattie, W. Zhou, M. O. Robinson, L. Harrington, Mol. Cell. Biol.21, 6151 (2001). (10.1128/MCB.21.18.6151-6160.2001) / Mol. Cell. Biol. (2001)
K. Arai et al., J. Biol. Chem.277, 8538 (2002). (10.1074/jbc.M111068200) / J. Biol. Chem. (2002)
Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr.
We thank the laboratory of T. Bryan (Cell Biology Unit Children's Medical Research Institute) for assistance with telomerase methods and L. Cheong L. Lu and T. Phan (Commonwealth Scientific and Industrial Research Organisation) for fermentation support. This research was supported by the Carcinogenesis Fellowship of the Cancer Council of New South Wales and by the National Health and Medical Research Council of Australia. The accession numbers for hTERT and human dyskerin are O14746 and CAA11970 respectively.

Dates

Type	When
Created	17 years, 9 months ago (Nov. 12, 2007, 5:49 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 3:14 a.m.)
Indexed	4 days, 1 hour ago (Aug. 29, 2025, 6 a.m.)
Issued	18 years, 5 months ago (March 30, 2007)
Published	18 years, 5 months ago (March 30, 2007)
Published Print	18 years, 5 months ago (March 30, 2007)

Funders 0

None

BibTeX

@article{Cohen_2007, title={Protein Composition of Catalytically Active Human Telomerase from Immortal Cells}, volume={315}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1138596}, DOI={10.1126/science.1138596}, number={5820}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Cohen, Scott B. and Graham, Mark E. and Lovrecz, George O. and Bache, Nicolai and Robinson, Phillip J. and Reddel, Roger R.}, year={2007}, month=mar, pages={1850–1853} }

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