The catalytic subunit of yeast telomerase

被引:198
作者
Counter, CM
Meyerson, M
Eaton, EN
Weinberg, RA
机构
[1] MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142
[2] MIT,DEPT BIOL,CAMBRIDGE,MA 02142
[3] MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114
关键词
telomeres; reverse transcriptase;
D O I
10.1073/pnas.94.17.9202
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 an RNA-directed DNA polymerase, composed of RNA and protein subunits, that replicates the telomere ends of linear eukaryotic chromosomes. Using a genetic strategy described here, we identify the product of the EST2 gene, Est2p, as a subunit of telomerase in the yeast Saccharomyces cerevisiae. Est2p is required for enzyme catalysis, as mutations in EST2 mere found to result in the absence of telomerase activity, Immunochemical experiments show that Est2p is an integral subunit of the telomerase enzyme. Critical catalytic residues present in RNA-directed DNA polymerases are conserved in Est2p; mutation of one such residue abolishes telomerase activity, suggesting a direct catalytic role for Est2p.
引用
收藏
页码:9202 / 9207
页数:6
相关论文
共 41 条
[1]  
Avilion AA, 1996, CANCER RES, V56, P645
[2]   THE MOLECULAR-STRUCTURE OF CENTROMERES AND TELOMERES [J].
BLACKBURN, EH ;
SZOSTAK, JW .
ANNUAL REVIEW OF BIOCHEMISTRY, 1984, 53 :163-194
[3]   Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis [J].
Blasco, MA ;
Rizen, M ;
Greider, CW ;
Hanahan, D .
NATURE GENETICS, 1996, 12 (02) :200-204
[4]   LARGE-SCALE ANALYSIS OF GENE-EXPRESSION, PROTEIN LOCALIZATION, AND GENE DISRUPTION SACCHAROMYCES-CEREVISIAE [J].
BURNS, N ;
GRIMWADE, B ;
ROSSMACDONALD, PB ;
CHOI, EY ;
FINBERG, K ;
ROEDER, GS ;
SNYDER, M .
GENES & DEVELOPMENT, 1994, 8 (09) :1087-1105
[5]   ORGANIZATION OF DNA-SEQUENCES AND REPLICATION ORIGINS AT YEAST TELOMERES [J].
CHAN, CSM ;
TYE, BK .
CELL, 1983, 33 (02) :563-573
[6]   TELOMERASE IN YEAST [J].
COHN, M ;
BLACKBURN, EH .
SCIENCE, 1995, 269 (5222) :396-400
[7]   PURIFICATION OF TETRAHYMENA TELOMERASE AND CLONING OF GENES ENCODING THE 2 PROTEIN-COMPONENTS OF THE ENZYME [J].
COLLINS, K ;
KOBAYASHI, R ;
GREIDER, CW .
CELL, 1995, 81 (05) :677-686
[8]   TELOMERASE ACTIVITY IN HUMAN OVARIAN-CARCINOMA [J].
COUNTER, CM ;
HIRTE, HW ;
BACCHETTI, S ;
HARLEY, CB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) :2900-2904
[9]   TELOMERE SHORTENING ASSOCIATED WITH CHROMOSOME INSTABILITY IS ARRESTED IN IMMORTAL CELLS WHICH EXPRESS TELOMERASE ACTIVITY [J].
COUNTER, CM ;
AVILION, AA ;
LEFEUVRE, CE ;
STEWART, NG ;
GREIDER, CW ;
HARLEY, CB ;
BACCHETTI, S .
EMBO JOURNAL, 1992, 11 (05) :1921-1929
[10]   THE RNA COMPONENT OF HUMAN TELOMERASE [J].
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 .
SCIENCE, 1995, 269 (5228) :1236-1241