Break-induced replication mechanisms in yeast and mammals

Break-induced replication (BIR) is a pathway specialized in repair of double-strand DNA breaks with only one end capable of invading homologous template that can arise following replication collapse, telomere erosion or DNA cutting by site-specific endonucleases. For a long time, yeast remained the only model system to study BIR. Studies in yeast demonstrated that BIR represents an unusual mode of DNA synthesis that is driven by a migrating bubble and leads to conservative inheritance of newly synthesized DNA. This unusual type of DNA synthesis leads to high levels of mutations and chromosome rearrangements. Recently, multiple examples of BIR were uncovered in mammalian cells that allowed the comparison of BIR between organisms. It appeared initially that BIR in mammalian cells is predominantly independent of RAD51, and therefore different from BIR that is predominantly Rad51-dependent in yeast. However, a series of systematic studies utilizing site-specific DNA breaks for BIR initiation in mammalian reporters led to the discovery of highly efficient RAD51-dependent BIR, allowing side-by side comparison with BIR in yeast which is the focus of this review.