Major cutbacks at chromosome ends

被引:76
作者
Lansdorp, PM [1 ]
机构
[1] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[2] Univ British Columbia, Dept Med, Vancouver, BC V5Z 4E3, Canada
关键词
D O I
10.1016/j.tibs.2005.05.004
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
To distinguish a telomere from a double-strand break, a minimum number of telomere repeats must 'cap' each chromosome end. The length of each repeat array will reflect a unique history of addition and losses. Telomere losses are predicted to occur slowly but surely with every replication cycle (referred to as 'typical' telomere loss) in addition to intermittently and, potentially, rapidly ('sporadic'). Recent studies have shown that sporadic telomere losses can result from failure to properly repair (oxidative) damage to telomeric DNA, from failure to properly process higher-order structures of G-rich DNA and from homologous recombination reactions. Differences in telomere-erosion pathways between normal and malignant cells provide novel targets for the prevention and therapy of disease.
引用
收藏
页码:388 / 395
页数:8
相关论文
共 86 条
[1]   A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length [J].
Askree, SH ;
Yehuda, T ;
Smolikov, S ;
Gurevich, R ;
Hawk, J ;
Coker, C ;
Krauskopf, A ;
Kupiec, M ;
McEachern, MJM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (23) :8658-8663
[2]   Age dependent aneuploidy and telomere length of the human vascular endothelium [J].
Aviv, H ;
Khan, MY ;
Skurnick, J ;
Okuda, K ;
Kimura, M ;
Gardner, J ;
Priolo, L ;
Aviv, A .
ATHEROSCLEROSIS, 2001, 159 (02) :281-287
[3]   Strand-specific fluorescence in situ hybridization: the CO-FISH family [J].
Bailey, SM ;
Goodwin, EH ;
Cornforth, MN .
CYTOGENETIC AND GENOME RESEARCH, 2004, 107 (1-2) :14-17
[4]   Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells [J].
Bailey, SM ;
Brenneman, MA ;
Goodwin, EH .
NUCLEIC ACIDS RESEARCH, 2004, 32 (12) :3743-3751
[5]   Extensive allelic variation and ultrashort telomeres in senescent human cells [J].
Baird, DM ;
Rowson, J ;
Wynford-Thomas, D ;
Kipling, D .
NATURE GENETICS, 2003, 33 (02) :203-207
[6]   Pot1, the putative telomere end-binding protein in fission yeast and humans [J].
Baumann, P ;
Cech, TR .
SCIENCE, 2001, 292 (5519) :1171-1175
[7]   Switching and signaling at the telomere [J].
Blackburn, EH .
CELL, 2001, 106 (06) :661-673
[8]   Telomere shortening and tumor formation by mouse cells lacking telomerase RNA [J].
Blasco, MA ;
Lee, HW ;
Hande, MP ;
Samper, E ;
Lansdorp, PM ;
DePinho, RA ;
Greider, CW .
CELL, 1997, 91 (01) :25-34
[9]   Extension of life-span by introduction of telomerase into normal human cells [J].
Bodnar, AG ;
Ouellette, M ;
Frolkis, M ;
Holt, SE ;
Chiu, CP ;
Morin, GB ;
Harley, CB ;
Shay, JW ;
Lichtsteiner, S ;
Wright, WE .
SCIENCE, 1998, 279 (5349) :349-352
[10]   Cancer and ageing: Rival demons? [J].
Campisi, J .
NATURE REVIEWS CANCER, 2003, 3 (05) :339-349