Metazoan genomes contain thousands of sequence tracts that match the guanine-quadruplex (G4) DNA signature G3NxG3NxG3NxG3, a motif that is intrinsically mutagenic, probably because it can form secondary structures during DNA replication. We and others have previously shown that in C. elegans, the gene dog-1 is required to prevent deletion formation at these G4 sites (Chueng et al, Kruisselbrink et al). Here we provide a protocol to show how this feature can be used to isolate deletion alleles of many Caenorhabditis elegans genes.