DNA damage-induced signalling in ataxia-telangiectasia and related syndromes

Lavin, MF and Kozlov, S (2007) DNA damage-induced signalling in ataxia-telangiectasia and related syndromes. Radiotherapy And Oncology, 83 3: 231-237. doi:10.1016/j.radonc.2007.04.032


Author Lavin, MF
Kozlov, S
Title DNA damage-induced signalling in ataxia-telangiectasia and related syndromes
Journal name Radiotherapy And Oncology   Check publisher's open access policy
ISSN 0167-8140
Publication date 2007-01-01
Sub-type Article (original research)
DOI 10.1016/j.radonc.2007.04.032
Volume 83
Issue 3
Start page 231
End page 237
Total pages 7
Editor Overgaard, J.
Place of publication Clare, Amsterdam
Publisher Elsevier Ireland Ltd
Collection year 2008
Language eng
Subject 730107 Inherited diseases (incl. gene therapy)
C1
320799 Neurosciences not elsewhere classified
Abstract ATM, the protein mutated in the human genetic disorder ataxia-telangiectasia, functions by responding to radiation damage to DNA, primarily DNA double strand breaks (dsb), to reduce the risk of genome instability, cancer and neurodegeneration. ATM is rapidly activated as an existing protein to phosphorylate a number of downstream proteins that are involved in DNA repair and cell cycle checkpoint activation. While the exact mechanism of activation of ATM has not been determined, it is now evident that it relies heavily on the Mre11 complex (Mre11 /Rad50/Nbs1) and a series of post-translational events for this activation. The Mre11 complex acts as a sensor for the break, recruits ATM to this site where it is autophosphorylated and then is capable of phosphorylating substrates that participate in DNA repair and cell cycle control. A greater understanding of how ATM is activated and functions through different signalling pathways is paramount to devising therapeutic strategies for the treatment of A-T patients. This knowledge can also be used to advantage in sensitizing cells to radiation and ultimately deriving novel therapeutic approaches for the treatment of cancer. (C) 2007 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 83 (2007) 231-237.
Keyword Oncology
Radiology, Nuclear Medicine & Medical Imaging
ataxia-tetangiectasia
ATM activation
autophosphorylation
celt cycle checkpoints
ionizing radiation
Nijmegen Breakage Syndrome
Atm Activation
Ionizing-radiation
Cellular-response
Mre11 Complex
In-vivo
P53
Protein
Autophosphorylation
Checkpoint
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Tue, 19 Feb 2008, 00:23:56 EST