DNA double-strand break (DSB) repair by homologous recombination is confined to the S and G phases of the cell cycle partly due to 53BP1 antagonizing DNA end resection in G phase and non-cycling quiescent (G) cells where DSBs are predominately repaired by non-homologous end joining (NHEJ). Unexpectedly, we uncovered extensive MRE11- and CtIP-dependent DNA end resection at DSBs in G murine and human cells. A whole genome CRISPR/Cas9 screen revealed the DNA-dependent kinase (DNA-PK) complex as a key factor in promoting DNA end resection in G cells.
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