To counteract damage to our genomes, numerous endo-and exonucleases incise the DNA backbone to remove damaged and aberrant DNA structures. It is imperative that such incisions be very tightly controlled, as unwanted DNA breaks are a key source of genome instability. Two new papers in The EMBO Journal shed light on how the activity of one such nuclease-ERCC1-XPF, an enzyme involved in various DNA repair pathways-is regulated to perform incision in the vicinity of DNA interstrand crosslinks.