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).


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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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1242/jcs.00740
ISSNs: 0021-9533 (print)
Related URLs:
Keywords: polyploidy, DNA repair, H2AX protein, Rad51 protein, mitotic catastrophe
ePrint ID: 26394
Date :
Date Event
Date Deposited: 19 Apr 2006
Last Modified: 16 Apr 2017 22:33
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/26394

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