The product of the gene (ATM) mutated in the human genetic disorder ataxia-telangiectasia (A-T) is a high molecular weight, protein ( approximately 350kDa) containing a C-terminal protein kinase domain and a number of other putative domains not yet functionally defined. The majority of ATM gene mutations in A-T patients are truncating, resulting in prematurely terminated products that are highly unstable. Missense mutations within the kinase domain and elsewhere in the molecule alter the stability of the protein and lead to loss of protein kinase activity. Only rarely are patients observed with two missense mutations and this gives rise to a milder disease phenotype. Evidence for a dominant interfering effect on normal ATM kinase activity has been reported in cell lines transfected with missense mutant ATM and in cell lines from some A-T heterozygotes. The dominant negative effect of mutant ATM is manifested by an enhancement of cellular radiosensitivity and may be responsible for the cancer predisposition observed in carriers of ATM missense mutations. In this review, we explore the domain structure of the ATM molecule, sites of interaction with other proteins and the consequences of specific amino acid changes on function.

Item Type:	Review Several Works
Keywords:	ATM gene, kinase activity
Research Division:	Biological Sciences
Research Group:	Biochemistry and cell biology
Research Field:	Biochemistry and cell biology not elsewhere classified
Objective Division:	Expanding Knowledge
Objective Group:	Expanding knowledge
Objective Field:	Expanding knowledge in the biological sciences
UTAS Author:	Gueven, N (Dr Nuri Guven)
ID Code:	79296
Year Published:	2004
Deposited By:	Pharmacy
Deposited On:	2012-08-29
Last Modified:	2019-02-15
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