Mice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging

被引:101
作者
Blasco, MA [1 ]
机构
[1] Spanish Natl Canc Ctr CNIO, Mol Oncol Program, Telomeres & Telomerase Grp, Madrid 28029, Spain
关键词
aging; cancer; mouse; telomerase; telomeres;
D O I
10.1038/sj.emboj.7600598
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Telomeres are capping structures at the ends of eukaryotic chromosomes, which consist of repetitive DNA bound to an array of specialized proteins. Telomeres are part of the constitutive heterochromatin and are subjected to epigenetic modifications. The function of telomeres is to prevent chromosome ends from being detected as damaged DNA. Both the length of telomere repeats and the integrity of the telomere-binding proteins are important for telomere protection. Telomere length is regulated by telomerase, by the telomere-binding proteins, as well as by activities that modify the state of the chromatin. Various mouse models with altered levels of telomerase activity, or mutant for different telomere-binding proteins, have been recently generated. Here, I will discuss how these different mouse models have contributed to our understanding on the role of telomeres and telomerase in cancer and aging.
引用
收藏
页码:1095 / 1103
页数:9
相关论文
共 118 条
[21]   Essential role of limiting telomeres in the pathogenesis of Werner syndrome [J].
Chang, S ;
Multani, AS ;
Cabrera, NG ;
Naylor, ML ;
Laud, P ;
Lombard, D ;
Pathak, S ;
Guarente, L ;
DePinho, RA .
NATURE GENETICS, 2004, 36 (08) :877-882
[22]   p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis [J].
Chin, L ;
Artandi, SE ;
Shen, Q ;
Tam, A ;
Lee, SL ;
Gottlieb, GJ ;
Greider, CW ;
DePinho, RA .
CELL, 1999, 97 (04) :527-538
[23]   A HUMAN TELOMERIC PROTEIN [J].
CHONG, L ;
VANSTEENSEL, B ;
BROCCOLI, D ;
ERDJUMENTBROMAGE, H ;
HANISH, J ;
TEMPST, P ;
DELANGE, T .
SCIENCE, 1995, 270 (5242) :1663-1667
[24]   Mammalian telomeres and telomerase [J].
Collins, K .
CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (03) :378-383
[25]   Telomerase in the human organism [J].
Collins, K ;
Mitchell, JR .
ONCOGENE, 2002, 21 (04) :564-579
[26]   Functional interaction between poly(ADP-ribose) polymerase 2 (PARP-2) and TRF2:: PARP activity negatively regulates TRF2 [J].
Dantzer, F ;
Giraud-Panis, MJ ;
Jaco, I ;
Amé, JC ;
Schultz, I ;
Blasco, M ;
Koering, CE ;
Gilson, E ;
Ménissier-de Murcia, J ;
de Murcia, G ;
Schreiber, V .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (04) :1595-1607
[27]   T-loops and the origin of telomeres [J].
de Lange, T .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (04) :323-329
[28]   Protection of mammalian telomeres [J].
de Lange, T .
ONCOGENE, 2002, 21 (04) :532-540
[29]   Telomere maintenance by recombination in human cells [J].
Dunham, MA ;
Neumann, AA ;
Fasching, CL ;
Reddel, RR .
NATURE GENETICS, 2000, 26 (04) :447-450
[30]   Resolution of sister telomere association is required for progression through mitosis [J].
Dynek, JN ;
Smith, S .
SCIENCE, 2004, 304 (5667) :97-100