Abstract
The faithful repair of DNA damage, especially chromosomal double-strand breaks (DSBs), is crucial for genomic integrity. We have previously shown that securin interacts with the Ku70/80 heterodimer of the DSB non-homologous DNA end-joining (NHEJ) repair machinery. Here we demonstrate that securin deficiency compromises cell survival and proliferation, but only after genotoxic stress. Securin−/− cells show a significant increase in gross chromosomal rearrangements and chromatid breaks after DNA damage, and also reveal an altered pattern of end resection in an NHEJ assay in comparison with securin+/+ cells. These data suggest that securin has a key role in the maintenance of genomic stability after DNA damage, thereby providing a previously unknown mechanism for regulating tumour progression.
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Abbreviations
- Adr:
-
adriamycin
- BrdU:
-
bromodeoxyuridine
- CPT:
-
camptothecin
- DSB:
-
double-strand break
- GCR:
-
gross chromosomal rearrangement
- HR:
-
homologous recombination
- IR:
-
ionizing radiation
- MMS:
-
methyl methanesulphonate
- NHEJ:
-
non-homologous DNA end joining
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Acknowledgements
We are grateful to AD Jeyasekharan for helping in the English edition of the manuscript, and to B Vogelstein for HCT116 sec−/− cells, to J Sánchez for advice on chromosomal analysis and M Shivji for critical reading of the manuscript. JAP-T and MT were supported by grants from the Spanish Ministerio de Ciencia y Tecnología and the DGUI of the Junta de Andalucía. CM-V is a recipient of a postdoctoral contract (Program Juan de la Cierva) from the Spanish Ministerio de Educación y Ciencia.
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Bernal, J., Roche, M., Méndez-Vidal, C. et al. Proliferative potential after DNA damage and non-homologous end joining are affected by loss of securin. Cell Death Differ 15, 202–212 (2008). https://doi.org/10.1038/sj.cdd.4402254
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DOI: https://doi.org/10.1038/sj.cdd.4402254
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