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Endopolyploid cells produced after severe genotoxic damage have the potential to repair DNA double strand breaks

Ivanov, Andrei, Cragg, Mark S., Erenpreisa, Jekaterina, Emzinsh, Dzintars, Lukman, Henny and Illidge, Timothy M. (2003) Endopolyploid cells produced after severe genotoxic damage have the potential to repair DNA double strand breaks Journal of Cell Science, 116, (20), pp. 4095-4106. (doi:10.1242/jcs.00740).

Record type: Article

Abstract

p53 mutant tumour cells respond to genotoxic insults by bypassing G1 arrest and halting in G2. Following release from G2 arrest they undergo mitotic catastrophe, whereby mitotic cycling is suppressed, delayed apoptosis begins and endopolyploid cells are produced. The ability of these endopolyploid cells to participate in the restitution process is controversial. To facilitate recovery, these endopolyploid cells must repair the extensive DNA damage induced. DNA damage and its resolution were studied by observing the kinetics of {gamma}-H2AX foci formation and by comet assay analysis. Subsequently, the kinetics and distribution of Rad51 foci were studied as a measure of homologous recombination. Here we present evidence of the resolution of DNA damage in endopolyploid cells through a decrease of tail moment by comet assay and in the number of cells expressing {gamma}-H2AX foci. Rad51 foci expression reached a maximum in endopolyploid cells on days 5-6 after irradiation, when delayed apoptosis was maximal, indicating that cells were being selected for survival at this time. Furthermore, the proportion of Annexin-V-positive polyploid cells decreased as they continued ongoing rounds of DNA replication, suggesting endoreduplication is involved in selecting cells resistant to apoptosis. Our findings suggest that after severe genotoxic insult endopolyploid cells have a transient survival advantage that may contribute to radioresistance of tumours that undergo mitotic catastrophe.

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More information

Published date: 2003
Keywords: polyploidy, DNA repair, H2AX protein, Rad51 protein, mitotic catastrophe

Identifiers

Local EPrints ID: 26394
URI: http://eprints.soton.ac.uk/id/eprint/26394
ISSN: 0021-9533
PURE UUID: d12c32e1-1555-4597-ae3c-bd78c258e246
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 19 Apr 2006
Last modified: 17 Jul 2017 16:07

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Contributors

Author: Andrei Ivanov
Author: Mark S. Cragg ORCID iD
Author: Jekaterina Erenpreisa
Author: Dzintars Emzinsh
Author: Henny Lukman
Author: Timothy M. Illidge

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