In Drosophila melanogaster, the conserved 3' → 5’ DNA helicases Bloom (BLM) and HELQ (DmMus301) have important roles in the maintenance of genomic stability, specifically in the repair of DNA double-strand breaks during homologous recombination. The Bloom helicase has both Holliday Junction dissolvase and D-loop/Rad51 filament disruptase activity, which both promote genomic stability by suppressing promiscuous crossover events and inappropriate strand invasion (recombination between regions of homeology, etc). DmMus301 mutants are deficient in both meiotic and mitotic break repair, and its human orthologue, HELQ, is involved in recombinational repair of double strand breaks. In this study, a synthetic larval-stage lethality between blm and mus301 mutants was identified and analyzed. A mus301 mutant lacking the helicase domain was combined with two different blm mutant alleles. The blmN1 mutant consists of a deletion which interrupts the helicase domain; the blmN2 mutant has a smaller deletion within the second exon, and does not interrupt the helicase domain. Crosses generating blmN1, mus301 and blmN2, mus301 double mutants produced both viable and synthetically lethal double mutant isolates for each combination of alleles. Interestingly, the timing of the lethality occurred at an earlier larval stage in the blmN2, mus301 double mutants, consistent with a dominant negative effect with the helicase-possessing BLM protein. We hypothesize that a third mutation on the mus301 chromosome is responsible for the synthetic lethality and are currently using whole genome sequencing to identify this mutation. Taken together, our data suggest there are novel roles for the BLM and HELQ helicases outside of their functions in homologous recombination repair. Furthermore, the identification of a third mutation which causes the observed larval lethality in blm, mus301 mutants will provide additional insight about their roles in maintaining genomic integrity.