ATM is required for the cellular response to thymidine induced replication fork stress

Bolderson, Emma, Scorah, Jennifer, Helleday, Thomas, Smythe, Carl, & Meuth, Mark (2004) ATM is required for the cellular response to thymidine induced replication fork stress. Human Molecular Genetics, 13(23), pp. 2937-2945.

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Genetically distinct checkpoints, activated as a consequence of either DNA replication arrest or ionizing radiation-induced DNA damage, integrate DNA repair responses into the cell cycle programme. The ataxia-telangiectasia mutated (ATM) protein kinase blocks cell cycle progression in response to DNA double strand breaks, whereas the related ATR is important in maintaining the integrity of the DNA replication apparatus. Here, we show that thymidine, which slows the progression of replication forks by depleting cellular pools of dCTP, induces a novel DNA damage response that, uniquely, depends on both ATM and ATR. Thymidine induces ATM-mediated phosphorylation of Chk2 and NBS1 and an ATM-independent phosphorylation of Chk1 and SMC1. AT cells exposed to thymidine showed decreased viability and failed to induce homologous recombination repair (HRR). Taken together, our results implicate ATM in the HRR-mediated rescue of replication forks impaired by thymidine treatment.

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ID Code: 60138
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
DOI: 10.1093/hmg/ddh316
ISSN: 0964-6906
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Biochemistry and Cell Biology not elsewhere classified (060199)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2004 Oxford University Press
Copyright Statement: Human Molecular Genetics, Vol. 13, No. 23 © Oxford University Press 2004; all rights reserved
Deposited On: 23 May 2013 22:22
Last Modified: 30 Jan 2015 05:07

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