Functional consequences of sequence alterations in the ATM gene

Lavin, Martin F., Scott, Shaun, Gueven, Nuri, Kozlov, Sergei, Peng, Cheng and Chen, Philip (2004) Functional consequences of sequence alterations in the ATM gene. DNA Repair, 3 8-9: 1197-1205. doi:10.1016/j.dnarep.2004.03.011

Author Lavin, Martin F.
Scott, Shaun
Gueven, Nuri
Kozlov, Sergei
Peng, Cheng
Chen, Philip
Title Functional consequences of sequence alterations in the ATM gene
Journal name DNA Repair   Check publisher's open access policy
ISSN 1568-7864
Publication date 2004-08
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.dnarep.2004.03.011
Volume 3
Issue 8-9
Start page 1197
End page 1205
Total pages 9
Editor E. C. Friedberg
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2004
Language eng
Abstract The product of the gene (ATM) mutated in the human genetic disorder ataxia-telangiectasia (A-T) is a high molecular weight, protein (similar to350 kDa) 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. (C) 2003 Elsevier B.V. All rights reserved.
Keyword Genetics & heredity
Atm Gene
Missense Mutations
Functional Domains
Radiation Signaling
Ataxia-telangiectasia Heterozygotes
Double-strand Break
S-phase Checkpoint
Induced Dna-damage
Genome Stability
Mutated Protein
Cancer Families
Mre11 Complex
Q-Index Code C1
Additional Notes This document is a journal review.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
2005 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 26 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 26 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 03:24:11 EST