Break-Induced Replication Repair of Damaged Forks Induces Genomic Duplications in Human Cells

In human cancers, oncogene activation interferes with DNA replication, leading to DNA replication stress and DNA double-strand breaks (DSBs). Costantino et al. (p. [88][1], published online 5 December) identified two subunits of DNA polymerase delta, POL3 and POL4, as critical for survival of DNA replication stress in human cells. Both subunits were required for break-induced replication (BIR), which is required to repair a specific type of DSB, with both subunits possibly required for processive DNA synthesis in BIR. Tandem head-to-tail duplications and fold-back inversions were seen in replication-stressed cells, similar to those seen in human breast and ovarian cancers, suggesting that BIR is important for repairing damaged forks in cancer cells. [1]: /lookup/doi/10.1126/science.1243211