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

Abstract

DNA Damage Repair 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 , 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.