Abstract
Essential to the viability of eukaryotic cells is their ability to efficiently and accurately repair DNA double-strand breaks (DSBs), which occur frequently through both exogenous and endogenous means. Mutations at the DNA level represent the main cause of heritable disease and cancer in humans, and as a result cells have highly conserved systems that ensure the fidelity of the genetic material. Cells possess an extensive competitive hierarchy of repair mechanisms that are differentially activated in specific instances and stages of the cell cycle. While gene conversion (GC) is generally the preferred mechanism to repair DSBs, break-induced replication (BIR) is an efficient process when only one end of homology to the DSB exists. Much recent interest has been invested in BIR, as it may be an important process in maintaining genomic integrity during S-phase replication by restarting arrested or collapsed replication forks. In addition, its ability to elongate telomeres in the absence of telomerase may be implicated in the immortalization of certain cancer cell lines. In this study, we explore whether SIR is any ditierent in its mutagenic properties compared to normalS-phase replication. Using a system previously employed to study BIR, we show that SIR is significantly more mutagenic than Sphase replication. Furthermore, we establish that mismatch repair (MMR), and potentially other DNA repair mechanisms, may be involved in BIR. The findings of this study contribute to our overall understanding of BIR., as well as its relative position in the hierarchy of DNA repair pathways.