Protein composition of catalytically active human telomerase from immortal cells

被引:514
作者
Cohen, Scott B.
Graham, Mark E.
Lovrecz, George O.
Bache, Nicolai
Robinson, Phillip J.
Reddel, Roger R.
机构
[1] Childrens Med Res Inst, Canc Res Unit, Westmead, NSW 2145, Australia
[2] Childrens Med Res Inst, Cell Signalling Unit, Westmead, NSW 2145, Australia
[3] CSIRO, Mol & Hlth Technol, Fermentat Lab, Parkville, Vic 3052, Australia
[4] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark
关键词
D O I
10.1126/science.1138596
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Telomerase is a ribonucleoprotein enzyme complex that adds 5'-TTAGGG-3' repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for similar to 90% of human cancers. We have purified human telomerase similar to 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.
引用
收藏
页码:1850 / 1853
页数:4
相关论文
共 19 条
  • [1] Two independent regions of human telomerase reverse transcriptase are important for its oligomerization and telomerase activity
    Arai, K
    Masutomi, K
    Khurts, S
    Kaneko, S
    Kobayashi, K
    Murakami, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (10) : 8538 - 8544
  • [2] Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita
    Armanios, M
    Chen, JL
    Chang, YPC
    Brodsky, RA
    Hawkins, A
    Griffin, CA
    Eshleman, JR
    Cohen, AR
    Chakravarti, A
    Hamosh, A
    Greider, CW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (44) : 15960 - 15964
  • [3] Functional multimerization of the human telomerase reverse transcriptase
    Beattie, TL
    Zhou, W
    Robinson, MO
    Harrington, L
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (18) : 6151 - 6160
  • [4] Telomere length dynamics in telomerase-positive immortal human cell populations
    Bryan, TM
    Englezou, A
    Dunham, MA
    Reddel, RR
    [J]. EXPERIMENTAL CELL RESEARCH, 1998, 239 (02) : 370 - 378
  • [5] THE RNA COMPONENT OF HUMAN TELOMERASE
    FENG, JL
    FUNK, WD
    WANG, SS
    WEINRICH, SL
    AVILION, AA
    CHIU, CP
    ADAMS, RR
    CHANG, E
    ALLSOPP, RC
    YU, JH
    LE, SY
    WEST, MD
    HARLEY, CB
    ANDREWS, WH
    GREIDER, CW
    VILLEPONTEAU, B
    [J]. SCIENCE, 1995, 269 (5228) : 1236 - 1241
  • [6] IDENTIFICATION OF A SPECIFIC TELOMERE TERMINAL TRANSFERASE-ACTIVITY IN TETRAHYMENA EXTRACTS
    GREIDER, CW
    BLACKBURN, EH
    [J]. CELL, 1985, 43 (02) : 405 - 413
  • [7] TELOMERES SHORTEN DURING AGING OF HUMAN FIBROBLASTS
    HARLEY, CB
    FUTCHER, AB
    GREIDER, CW
    [J]. NATURE, 1990, 345 (6274) : 458 - 460
  • [8] X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions
    Heiss, NS
    Knight, SW
    Vulliamy, TJ
    Klauck, SM
    Wiemann, S
    Mason, PJ
    Poustka, A
    Dokal, I
    [J]. NATURE GENETICS, 1998, 19 (01) : 32 - 38
  • [9] Purification of telomerase from Euplotes aediculatus: Requirement of a primer 3' overhang
    Lingner, J
    Cech, TR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (20) : 10712 - 10717
  • [10] Reverse transcriptase motifs in the catalytic subunit of telomerase
    Lingner, J
    Hughes, TR
    Shevchenko, A
    Mann, M
    Lundblad, V
    Cech, TR
    [J]. SCIENCE, 1997, 276 (5312) : 561 - 567