Blm Helicase Facilitates Rapid Replication of Repetitive DNA Sequences in early Drosophila Development

The absence of functional BLM DNA helicase, a member of the RecQ family of helicases, is responsible for the rare human disorder Bloom Syndrome, which results in developmental abnormalities, DNA repair defects, genomic instability, and a predisposition to cancer. In Drosophila melanogaster, the orthologous Blm protein is essential during early development when the embryo is under the control of maternal gene products. A lack of functional maternal Blm during the syncytial cell cycles of Drosophila embryonic development results in severe nuclear defects and lethality. An investigation of the specific role Blm plays during this developmental stage revealed that, amongst the small fraction of embryos from Blm mutant mothers that survive, a prominent sex-bias favors the class of flies that inherits less repetitive DNA content, which serves as an endogenous source of replication stress. We show that this selection against repetitive DNA content reflects a role for Blm in facilitating replication through these repetitive sequences during the rapid replication cycles of syncytial development. During this developmental stage, Blm is not required for its role in complex DNA repair; however, the sex-bias that results from the absence of maternal Blm is exacerbated by repetitive DNA sequences, suggesting that the essential role for Blm during this stage is in managing replication fork stress brought about by factors that may impede fork progression. Additionally, our data suggest that Blm is only required to manage this replication stress during embryonic development, and likely only during the early, rapid syncytial cell cycles, and not at later developmental stages. These results provide novel insights into Blm function throughout development.