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FRA16D common chromosomal fragile site oxido-reductase (FOR/WWOX) protects against the effects of ionizing radiation in Drosophila

Oncogene volume 24, pages 6590–6596 (2005)Cite this article

A Corrigendum to this article was published on 07 December 2006

Abstract

Fragile sites are chromosomal structures that have been proposed to have a determining role in cancer-associated DNA instability. The human WWOX gene spans the FRA16D chromosomal fragile site, the common minimal region of homozygous deletion found in adenocarcinomas and three out of five translocation breakpoints in multiple myeloma. Transcripts from the alternatively spliced WWOX gene encode proteins with common N-terminal WW domains and variable homology to the oxidoreductase family of proteins. In this study, the Drosophila orthologue of the WWOX gene was identified and subjected to mutagenesis via homologous recombination. The resultant DmWWOX1 mutants were viable but exhibited an increased sensitivity to ionizing radiation. This radiation sensitivity was rescued by reintroduction and expression of either the wild-type Drosophila or human WWOX genes. Thus, the protective function of DmWWOX in response to irradiation in Drosophila is conserved with human WWOX (hWWOX). This is consistent with a protective role for hWWOX where aberrant expression, as a result of breakage at the associated fragile site, could contribute directly to cancer progression.

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Acknowledgements

We would like to thank V Evci and J Mackrill for technical assistance, the IMVS Transfusion Medicine Unit for the kind use of their irradiation machine and members of the Richards lab for their constructive comments on drafts of this manuscript. This work was supported, in part, by grant (207809) from the National Health and Medical Research Council, Australia to RIR and the ARC Special Research Centre for the Molecular Genetics of Development from the Australian Research Council to RIR and RBS. LVO is the recipient of a Peter Doherty Post-doctoral Research Fellowship (207830) from the National Health and Medical Research Council, Australia.

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  1. ARC Special Research Centre for the Molecular Genetics of Development, The University of Adelaide, Adelaide, 5005, SA, Australia

    Louise V O'Keefe, Yinghong Liu, Alison Perkins, Sonia Dayan, Robert Saint & Robert I Richards

  2. ARC-NHMRC Research Network in Genes and Environment in Development, School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide, 5005, SA, Australia

    Robert Saint & Robert I Richards

  3. Research School of Biological Sciences, Australian National University, Canberra, ACT 2601, Australia

    Robert Saint

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  1. Louise V O'Keefe
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Correspondence to Robert I Richards.

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O'Keefe, L., Liu, Y., Perkins, A. et al. FRA16D common chromosomal fragile site oxido-reductase (FOR/WWOX) protects against the effects of ionizing radiation in Drosophila. Oncogene 24, 6590–6596 (2005). https://doi.org/10.1038/sj.onc.1208806

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