Mitosis Inhibits DNA Double-Strand Break Repair to Guard Against Telomere Fusions

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Science  11 Apr 2014:
Vol. 344, Issue 6180, pp. 189-193
DOI: 10.1126/science.1248024

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Shutting Down Repair to Protect

Cells repair DNA double-strand breaks (DSBs) by halting the cell cycle and activating the machinery involved in mending the breaks. However, during mitosis neither the DNA damage checkpoint nor DSB repair occur, apparently leaving the cell extremely vulnerable to DSBs. Orthwein et al. (p. 189, published online 20 March) found that the DSB response was blocked by the phosphorylation of two crucial repair factors, RNF8 and PB531, preventing their recruitment to the site of damage. Restoring DSB repair during mitosis caused end-to-end chromosome fusions, which are catastrophic for chromosome segregation and normal cell division, explaining why the repair machinery is shut down during cell division.