Ataxia telangiectasia mutated

Ataxia telangiectasia mutated (ATM), poly(ADP ribose) polymerase (PARP), DNA-dependent protein kinase, DNA replication factor C, DNA topoisomerase I, DNA fragmentation factor (DFF)45, inhibitor of caspase-activated DNAse (ICAD), lamins A, Bl, and C TRAF-1, Rafl, Ras, GAP, GDP dissociation inhibitor of Rho family GTPases, phospholipase A2, Statl... 

ATM Ataxia telangiectasia mutated. Kinase, plays a key role in repair of double-stranded DNA breaks. 

SI39 (for mammals). The responsible kinases are members from phosphatidyli-nositol 3-kinase (PI3K)-like family kinases, which include ataxia telangiectasia mutated (ATM), AT-related (ATR), and DNA dependent protein kinase (DNA-PK) (Burma et al, 2001 Stiff et al, 2004 van Attikum and Gasser, 2005). Histone H2AX phosphorylation is directly related to repair of damaged chromatin (for details see chapter on Role of histone phosphorylation in chromatin dynamics and its implication in diseases ). 

Ataxia telangiectasia Mutation in gene on chromosome 11, which codes for protein involved in signal transduction, DNA repair, and control of cell cycle. Defect in cell-mediated immunity. Cerebral ataxia and telangiectasias are hallmarks. 

The ATM protein has been identified as an important member of a reaction chain that leads from detection of DNA damage to activation of the p53 protein. Mutations of the ATM protein are causally associated with the disease ataxia telangiectasia, thus the name ATM (ataxia telangiectasia mutated). The ATM protein has protein kinase activity and is counted as a member of the PI3-kinase family, due to sequence homologies (review Canman et al., 1998). The p53 protein is phosphorylated at Serl5 by ATM kinase (Canman et al., 1998) and it is assumed that this phosphorylation contributes to activation of the p53 protein. The ATM protein is preceded by other protein kinases that are directly or indirectly activated by DNA damage and pass this signal on to the p53 protein via the ATM protein. 

Heiss EH, Schilder YD, Dirsch VM. 2007. Chronic treatment with resveratrol induces redox stress- and ataxia telangiectasia-mutated (ATM)-dependent senescence in p53-positive cancer cells. J Biol Chem 282 26759-26766. 

Individuals with the hereditary disorder ataxia telangiectasia suffer from neurodegeneration, immunodeficiency, and increased incidence of cancer. The genetic basis for ataxia telangiectasia is a loss-of-function mutation in the ATM gene (ATM = ataxia telangiectasia-mutated). Name two substrates of ATM. How does the phosphorylation of these substrates lead to inactivation of CDKs to enforce cell cycle arrest at a checkpoint ... 

Matsuoka, S., Rotman, G., Ogawa, A., Shiloh, Y, Tamai, K, Elledge, S. J. (2000). Ataxia telangiectasia-mutated phosphorylates chk2 in vivo and in vitro [in process citation]. Proceedings of... 

Rudolph, N. S., Latt, S. A. (1989). Flow cytometric analysis of X-ray sensitivity in ataxia telangiectasia. Mutation Research, 211, 31-41. 

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