A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity

Significance A DNA double-strand break (DSB) can be repaired accurately by homologous recombination. The Mre11-Rad50-Nbs1 (MRN) complex is responsible for initiating recombination degrading 5?-ended strand, where its activation the Ctp1 cofactor plays a pivotal role. Here, using purified fission yeast proteins, we show that two major elements comprise MRN activation. First, phosphorylation of promotes physical interaction between and Ctp1. Second, C terminus activates nucleolytic processing DSB ends. In latter case, small peptide comprising only 15 amino acids from sufficient to activate MRN. Our results elucidate core underlying