Lin, S. et al. eLife doi:10.7554/eLife.04766 (15 December 2014).

Cells use two strategies to repair a double-strand break (DSB) in their DNA: one, the joining of nonhomologous ends, leads to variable mutations; the other, homology-directed repair (HDR), uses a homologous donor to precisely repair the break. Targeted nucleases such as Cas9, which is part of the clustered, regularly interspaced, short palindromic repeats (CRISPR) system, induce such DSBs, but the rate of HDR is often low. Lin et al. reasoned that the simple synchronization of cell-cycle stages and the timed delivery of the Cas9–guide RNA complex would increase the rate of HDR. They transfected the Cas9 ribonucleoprotein complex into various cell types in late S or G2 phase—the only stages in which HDR occurs—and saw HDR-mediated editing levels of nearly 40%.