An Imperfect G(2)/M Checkpoint Contributes to Chromosome Instability Following Irradiation of S and G(2) Phase Cells

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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Abstract

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.

Item Type: Article
Schools and Departments: School of Life Sciences
Depositing User: Gee Wheatley
Date Deposited: 30 Sep 2008
Last Modified: 13 Mar 2017 12:03
URI: http://sro.sussex.ac.uk/id/eprint/1854
Google Scholar:43 Citations

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