Krempler, A., Deckbar, D., Jeggo, P.A. and Lobrich, M. (2007) An Imperfect G(2)/M Checkpoint Contributes to Chromosome Instability Following Irradiation of S and G(2) Phase Cells. Cell Cycle, 6 (14). pp. 1682-1686. ISSN 1551-4005
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DNA double strand break (DSB) repair and checkpoint control represent two major mechanisms that function to reduce chromosomal instability following ionizing irradiation (IR). Ataxia telangiectasia (A-T) cells have long been known to have defective checkpoint responses. Recent studies have shown that they also have a DSB repair defect following IR raising the issue of how ATM's repair and checkpoint functions interplay to maintain chromosomal stability. A-T and Artemis cells manifest an identical and epistatic repair defect throughout the cell cycle demonstrating that ATM's major repair defect following IR represents Artemis-dependent end-processing. Artemis cells show efficient G(2)/M checkpoint induction and a prolonged arrest relative to normal cells. Following irradiation of G(2) cells, this checkpoint is dependent on ATM and A-T cells fail to show checkpoint arrest. In contrast, cells irradiated during S phase initiate a G(2)/M checkpoint which is independent of ATM and, significantly, both Artemis and A-T cells show a prolonged arrest at the G(2)/M checkpoint likely reflecting their repair defect. Strikingly, the G(2)/M checkpoint is released before the completion of repair when approximately 10-20 DSBs remain both for S phase and G(2) phase irradiated cells. This defined sensitivity level of the G(2)/M checkpoint explains the prolonged arrest in repair-deficient relative to normal cells and provides a conceptual framework for the cooperative phenotype between checkpoint and repair functions in maintaining chromosomal stability.
|Schools and Departments:||School of Life Sciences|
|Depositing User:||Gee Wheatley|
|Date Deposited:||30 Sep 2008|
|Last Modified:||13 Mar 2017 12:03|
|Google Scholar:||43 Citations|