Enhancement of BLM-DNA2-Mediated Long-Range DNA End Resection by CtIP

Summary DNA double-strand break repair by homologous recombinationentails the resectionof DNA ends to reveal ssDNA tails, which are used to invade a homologous DNA template. CtIP and its yeast ortholog Sae2 regulate the nucleaseactivity of MRE11 in the initial stage of resection. Deletion of CtIP in the mouse or SAE2 in yeast engenders a more severe phenotype than MRE11 nucleaseinactivation, indicative of a broader role of CtIP/Sae2. Here, we provide biochemical evidence that CtIP promotes long-range resectionvia the BLM-DNA2 pathway. Specifically, CtIP interacts with BLM and enhances its helicaseactivity, and it enhances DNA cleavage by DNA2. Thus, CtIP influences multiple aspects of end resectionbeyond MRE11 regulation.