The telomerase cycle:: normal and pathological aspects

被引:17
作者
Brunori, M
Luciano, P
Gilson, E
Géli, V
机构
[1] CNRS, Lab Ingn Syst Macromol, F-13402 Marseille, France
[2] Ecole Normale Lyon, CNRS,UMR 5161, INRA U1237, Lab Biol Mol Cellule, F-69364 Lyon, France
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2005年 / 83卷 / 04期
关键词
telomerase; chromatin; telomere capping; DNA repair; senescence;
D O I
10.1007/s00109-004-0616-2
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Telomeres are nucleoprotein complexes that cap the end of eukaryotic chromosomes and are essential for their function and stability. Telomerase, a reverse transcriptase that extends the single-stranded G-rich 3' protruding ends of chromosomes, stabilizes telomere length in germ line cells and regenerative tissues as well as in tumor cells. In the absence of telomerase telomeres shorten with cell division, a process able to trigger cell growth arrest. When telomerase is present in the cell, its activity is tightly regulated at its site of action by factors specifically bound to the telomeric DNA. Recent data indicate that telomeres reorganize during the cell cycle. This review summarizes our current knowledge on how telomeres are dynamically organized and remodeled during cell cycle and stress response, pointing out the conservation and the difference between yeast and human. We then focus on the cellular consequences of telomere modifications in normal and cancer cells. This leads to a discussion of the different roles, seemingly contradictory, of telomeres and telomerase during the initiation and the progression of a cancer.
引用
收藏
页码:244 / 257
页数:14
相关论文
共 181 条
[51]   Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13 [J].
Grandin, N ;
Reed, SI ;
Charbonneau, M .
GENES & DEVELOPMENT, 1997, 11 (04) :512-527
[52]   Ten1 functions in telomere end protection and length regulation in association with Stn1 and Cdc13 [J].
Grandin, N ;
Damon, C ;
Charbonneau, M .
EMBO JOURNAL, 2001, 20 (05) :1173-1183
[53]   Yeast Ku as a regulator of chromosomal DNA end structure [J].
Gravel, S ;
Larrivée, M ;
Labrecque, P ;
Wellinger, RJ .
SCIENCE, 1998, 280 (5364) :741-744
[54]   Short dysfunctional telomeres impair tumorigenesis in the INK4aΔ2/3 cancer-prone mouse [J].
Greenberg, RA ;
Chin, L ;
Femino, A ;
Lee, KH ;
Gottlieb, GJ ;
Singer, RH ;
Greider, CW ;
DePinho, RA .
CELL, 1999, 97 (04) :515-525
[55]   TEL1, A GENE INVOLVED IN CONTROLLING TELOMERE LENGTH IN SACCHAROMYCES-CEREVISIAE, IS HOMOLOGOUS TO THE HUMAN ATAXIA-TELANGIECTASIA GENE [J].
GREENWELL, PW ;
KRONMAL, SL ;
PORTER, SE ;
GASSENHUBER, J ;
OBERMAIER, B ;
PETES, TD .
CELL, 1995, 82 (05) :823-829
[56]   Mammalian telomeres end in a large duplex loop [J].
Griffith, JD ;
Comeau, L ;
Rosenfield, S ;
Stansel, RM ;
Bianchi, A ;
Moss, H ;
de Lange, T .
CELL, 1999, 97 (04) :503-514
[57]   Pol12 the B subunit of DNA polymerase α, functions in both telomere capping and length regulation [J].
Grossi, S ;
Puglisi, A ;
Dmitriev, PV ;
Lopes, M ;
Shore, D .
GENES & DEVELOPMENT, 2004, 18 (09) :992-1006
[58]   Telomere formation by Rap1p binding site arrays reveals end-specific length regulation requirements and active telomeric recombination [J].
Grossi, S ;
Bianchi, A ;
Damay, P ;
Shore, D .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (23) :8117-8128
[59]   Inhibition of telomerase limits the growth of human cancer cells [J].
Hahn, WC ;
Stewart, SA ;
Brooks, MW ;
York, SG ;
Eaton, E ;
Kurachi, A ;
Beijersbergen, RL ;
Knoll, JHM ;
Meyerson, M ;
Weinberg, RA .
NATURE MEDICINE, 1999, 5 (10) :1164-1170
[60]   Creation of human tumour cells with defined genetic elements [J].
Hahn, WC ;
Counter, CM ;
Lundberg, AS ;
Beijersbergen, RL ;
Brooks, MW ;
Weinberg, RA .
NATURE, 1999, 400 (6743) :464-468