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XRCC3 Depletion Induces Spontaneous DNA Breaks and p53-Dependent Cell Death

Martin Loignon, Lilian Amrein, Michael Dunn and Raquel Aloyz

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In vertebrate cells, Xrcc3 initiates the repair of exogenous induced-DNA breaks during S and G2/M phases of the cell cycle by homologous recombination. However, much less is known of the role of Xrcc3 in the response to spontaneous DNA breaks. Using a siRNA approach, we show that depletion of XRCC3 inhibits the proliferation of MCF7 breast cancer cells. This inhibition of replication coincides with the accumulation of DNA breaks, as shown by the comet assay. Cell cycle specific analysis of γH2AX expression shows that S and G2/M phase cells express the highest fraction of γH2AX positive cells. This is consistent with replication-dependent accumulation of DNA breaks and deficient homologous recombination. While the induction of γH2AX is followed by cell death in parental cells, a p53 knockdown derivative becomes more resistant to XRCC3 depletion-induced death without changes in the levels of γH2AX. These results show that XRCC3 is required for the proliferation of MCF7 cells, and that decrease in its expression leads to the accumulation of DNA breaks and the induction of p53-dependent cell death.

Authors

Martin Loignon

McGill University, Montreal, Quebec, Canada

Lilian Amrein

McGill University, Montreal, Quebec, Canada

Michael Dunn

McGill University, Montreal, Quebec, Canada

Raquel Aloyz

McGill University, Montreal, Quebec, Canada

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.