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Functional consequences of sequence alterations in the ATM gene
Citation
Lavin, MF and Scott, S and Gueven, N and Kozlov, S and Peng, C and Chen, P, Functional consequences of sequence alterations in the ATM gene, D N A Repair, 3, (8-9) pp. 1197-205. ISSN 1568-7864 (2004) [Review Several Works]
Copyright Statement
Copyright 2004 Elsevier
Official URL: https://doi.org/10.1016/j.dnarep.2004.03.011
Abstract
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 Details
Item Type: | Review Several Works |
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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 |
Downloads: | 0 |
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