ATM and ataxia telangiectasia - Second in Molecular Medicine Review Series

被引:268
作者
McKinnon, PJ [1 ]
机构
[1] St Jude Childrens Res Hosp, Dept Genet & Tumor Cell Biol, Memphis, TN 38105 USA
关键词
ataxia telangiectasia; ATM; DNA damage; neurodegeneration;
D O I
10.1038/sj.embor.7400210
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
Ataxia telangiectasia ( AT) has long intrigued the biomedical research community owing to the spectrum of defects that are characteristic of the disease, including neurodegeneration, immune dysfunction, radiosensitivity and cancer predisposition. Following the identification of mutations in ATM ( ataxia telangiectasia, mutated) as the underlying cause of the disease, biochemical analysis of this protein kinase has shown that it is a crucial nexus for the cellular response to DNA double-stranded breaks. Many ATM kinase substrates are important players in the cellular responses that prevent cancer. Accordingly, AT is a disease that results from defects in the response to specific types of DNA damage. Thus, although it is a rare neurodegenerative disease, understanding the biology of AT will lead to a greater understanding of the fundamental processes that underpin cancer and neurodegeneration.
引用
收藏
页码:772 / 776
页数:5
相关论文
共 60 条
[31]   Oropharyngeal dysphagia and aspiration in patients with ataxia-telangiectasia [J].
Lefton-Greif, MA ;
Crawford, TO ;
Winkelstein, JA ;
Loughlin, GM ;
Koerner, CB ;
Zaburak, M ;
Lederman, HM .
JOURNAL OF PEDIATRICS, 2000, 136 (02) :225-231
[32]  
Lewis RF, 1999, ANN NEUROL, V46, P287, DOI 10.1002/1531-8249(199909)46:3<287::AID-ANA3>3.0.CO
[33]  
2-0
[34]   Critical role for Atm in suppressing V(D)J recombination-driven thymic lymphoma [J].
Liao, MJ ;
Van Dyke, T .
GENES & DEVELOPMENT, 1999, 13 (10) :1246-1250
[35]   The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin [J].
Moreira, MC ;
Barbot, C ;
Tachi, N ;
Kozuka, N ;
Uchida, E ;
Gibson, T ;
Mendonça, P ;
Costa, M ;
Barros, J ;
Yanagisawa, T ;
Watanabe, M ;
Ikeda, Y ;
Aoki, M ;
Nagata, T ;
Coutinho, P ;
Sequeiros, J ;
Koenig, M .
NATURE GENETICS, 2001, 29 (02) :189-193
[36]   DNA damage tumor suppressor genes and genomic instability [J].
Motoyama, N ;
Naka, K .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2004, 14 (01) :11-16
[37]   GENETICS RESEARCH - DISCOVERY OF AT GENE SPARKS BIOMEDICAL-RESEARCH BONANZA [J].
NOWAK, R .
SCIENCE, 1995, 268 (5218) :1700-1701
[38]   Immunodeficiency and infections in ataxia-telangiectasia [J].
Nowak-Wegrzyn, A ;
Crawford, TO ;
Winkelstein, JA ;
Carson, KA ;
Lederman, HM .
JOURNAL OF PEDIATRICS, 2004, 144 (04) :505-511
[39]   Sensing of intermediates in V(D)J recombination by ATM [J].
Perkins, EJ ;
Nair, A ;
Cowley, DO ;
Van Dyke, T ;
Chang, Y ;
Ramsden, DA .
GENES & DEVELOPMENT, 2002, 16 (02) :159-164
[40]  
Perlman Susan, 2003, Semin Pediatr Neurol, V10, P173, DOI 10.1016/S1071-9091(03)00026-3