Break-induced repair (BIR) is a homologous recombination pathway used to repair damaged replication forks in yeast. This paper examined whether the BIR pathway is active in human cells under conditions of DNA replication stress. Overexpression of cyclin E (a model of DNA replication stress in human cells) showed that POLD3 (the human orthologue of yeast Pol32, which is required for BIR) is needed for cell cycle progression and DNA synthesis during replication stress. Moreover, the DNA duplications that occurred in these cells during replication stress were dependent on POLD3 and BIR-mediated recombination. Thus, BIR might be used to repair collapsed replication forks in human cells and might explain the high levels of genomic duplications that are evident in human cancers.