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Mitotic death: a mechanism of survival? A review

Erenpreisa, Jekaterina and Cragg, M.S. (2001) Mitotic death: a mechanism of survival? A review Cancer Cell International, 1, (1) (doi:10.1186/1475-2867-1-1).

Record type: Article

Abstract

Mitotic death is a delayed response of p53 mutant tumours that are resistant to genotoxic damage. Questions surround why this response is so delayed and how its mechanisms serve a survival function. After uncoupling apoptosis from G1 and S phase arrests and adapting these checkpoints, p53 mutated tumour cells arrive at the G2 compartment where decisions regarding survival and death are made. Missed or insufficient DNA repair in G1 and S phases after severe genotoxic damage results in cells arriving in G2 with an accumulation of point mutations and chromosome breaks. Double strand breaks can be repaired by homologous recombination during G2 arrest. However, cells with excessive chromosome lesions either directly bypass the G2/M checkpoint, starting endocycles from G2 arrest, or are subsequently detected by the spindle checkpoint and present with the features of mitotic death. These complex features include apoptosis from metaphase and mitosis restitution, the latter of which can also facilitate transient endocycles, producing endopolyploid cells. The ability of cells to initiate endocycles during G2 arrest and mitosis restitution most likely reflects their similar molecular environments, with down-regulated mitosis promoting factor activity. Resulting endocycling cells have the ability to repair damaged DNA, and although mostly reproductively dead, in some cases give rise to mitotic progeny. We conclude that the features of mitotic death do not simply represent aberrations of dying cells but are indicative of a switch to amitotic modes of cell survival that may provide additional mechanisms of genotoxic resistance.

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More information

Published date: 2001
Additional Information: Review Article

Identifiers

Local EPrints ID: 26295
URI: http://eprints.soton.ac.uk/id/eprint/26295
ISSN: 1475-2867
PURE UUID: e4cb1322-387e-4def-883c-95f2515450fb
ORCID for M.S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 21 Apr 2006
Last modified: 17 Jul 2017 16:07

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Contributors

Author: Jekaterina Erenpreisa
Author: M.S. Cragg ORCID iD

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