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, which apparently leaves the cell extremely vulnerable to DSBs. Orthwein et al. found that the DSB response was blocked by the phosphorylation of two crucial repair factors, RNF8 and PB531, which prevented 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, and this explains why the repair machinery is shut down during cell division.
A. Orthwein, A. Fradet-Turcotte, S. M. Noordermeer, M. D. Canny, C. M. Brun, J. Strecker, C. Escribano-Diaz, D. Durocher, Mitosis inhibits DNA double-strand break repair to guard against telomere fusions. Science 344, 189–193 (2014). [Abstract] [Full Text]