ATM function and telomere stability

被引:136
作者
Pandita, TK [1 ]
机构
[1] Columbia Univ Coll Phys & Surg, Ctr Radiol Res, New York, NY 10032 USA
关键词
ATM; telomeres; telomerase; hTERT; DNA damage; signal transduction;
D O I
10.1038/sj.onc.1205060
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
Accumulation of DNA damage has been associated with the onset of senescence and predisposition to cancer. The gene responsible for ataxia telangiectasia (A-T) is ATM (ataxia-telangiectasia mutant), a master controller of cellular pathways and networks, orchestrating the responses to a specific type of DNA damage: the double strand break. Based on the homology of the human ATM gene to the TEL1, MEC1 and rad3 genes of yeast, it has now been demonstrated that mutations in ATM lead to defective telomere maintenance in mammalian cells. While ATM has both nuclear and cytoplasmic functions, this review will focus on its roles in telomere metabolism and how ATM and telomeres serve as controllers of cellular responses to DNA damage.
引用
收藏
页码:611 / 618
页数:8
相关论文
共 81 条
[1]   Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of cytokine receptor signaling [J].
Abraham, RT .
CURRENT OPINION IN IMMUNOLOGY, 1998, 10 (03) :330-336
[2]  
Agami R, 1999, NATURE, V399, P809
[3]   SYNAPTONEMAL COMPLEX-ASSOCIATED CENTROMERES AND RECOMBINATION NODULES IN PLANT MEIOCYTES PREPARED BY AN IMPROVED SURFACE-SPREADING TECHNIQUE [J].
ALBINI, SM ;
JONES, GH .
EXPERIMENTAL CELL RESEARCH, 1984, 155 (02) :588-592
[4]  
ANDEGEKO Y, 2001, IN PRESS J BIOL CHEM
[5]  
ASHLEY T, 1994, HUM GENET, V94, P587, DOI 10.1007/BF00206950
[6]  
Barlow C, 1998, DEVELOPMENT, V125, P4007
[7]   Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation [J].
Baskaran, R ;
Wood, LD ;
Whitaker, LL ;
Canman, CE ;
Morgan, SE ;
Xu, Y ;
Barlow, C ;
Baltimore, D ;
WynshawBoris, A ;
Kastan, MB ;
Wang, JYJ .
NATURE, 1997, 387 (6632) :516-519
[8]   STRUCTURE AND FUNCTION OF TELOMERES [J].
BLACKBURN, EH .
NATURE, 1991, 350 (6319) :569-573
[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]   Activation of the ATM kinase by ionizing radiation and phosphorylation of p53 [J].
Canman, CE ;
Lim, DS ;
Cimprich, KA ;
Taya, Y ;
Tamai, K ;
Sakaguchi, K ;
Appella, E ;
Kastan, MB ;
Siliciano, JD .
SCIENCE, 1998, 281 (5383) :1677-1679