DDX5 Regulates DNA Replication And Is Required For Cell Proliferation In A Subset Of Breast Cancer Cells
Menée sur des lignées cellulaires, cette étude met en évidence le rôle joué par un plasmide de l'épisome, DDX5, dans la régulation de la réplication de l'ADN et la prolifération de certaines cellules de cancer du sein
Understanding factors required for DNA replication will enrich our knowledge of this important process and potentially identify vulnerabilities that can be exploited in cancer therapy. We applied an assay that measures the stability of maintenance of an episomal plasmid in human tissue culture cells to screen for new DNA replication factors. We identify an important role for DDX5 in G1-to-S phase progression where it directly regulates DNA replication factor expression by promoting the recruitment of RNA Polymerase II to E2F-regulated gene promoters. We find that the DDX5 locus is frequently amplified in breast cancer and that breast cancer derived cells with amplification of DDX5 are much more sensitive to its depletion than breast cancer cells and a breast epithelial cell line that lack DDX5 amplification. Our results demonstrate a novel role for DDX5 in cancer cell proliferation and suggest DDX5 as a therapeutic target in breast cancer treatment.