Sakofsky, Cynthia J.Ayyar, SandeepMalkova, Anna2018-07-272018-07-272012-10-16Sakofsky, C. J., Ayyar, S., & Malkova, A. (2012). Break-Induced Replication and Genome Stability. Biomolecules, 2(4), 483–504. https://doi.org/10.3390/biom20404832218-273Xhttps://hdl.handle.net/1805/16853Genetic instabilities, including mutations and chromosomal rearrangements, lead to cancer and other diseases in humans and play an important role in evolution. A frequent cause of genetic instabilities is double-strand DNA breaks (DSBs), which may arise from a wide range of exogeneous and endogeneous cellular factors. Although the repair of DSBs is required, some repair pathways are dangerous because they may destabilize the genome. One such pathway, break-induced replication (BIR), is the mechanism for repairing DSBs that possesses only one repairable end. This situation commonly arises as a result of eroded telomeres or collapsed replication forks. Although BIR plays a positive role in repairing DSBs, it can alternatively be a dangerous source of several types of genetic instabilities, including loss of heterozygosity, telomere maintenance in the absence of telomerase, and non-reciprocal translocations. Also, mutation rates in BIR are about 1000 times higher as compared to normal DNA replication. In addition, micro-homology-mediated BIR (MMBIR), which is a mechanism related to BIR, can generate copy-number variations (CNVs) as well as various complex chromosomal rearrangements. Overall, activation of BIR may contribute to genomic destabilization resulting in substantial biological consequences including those affecting human health.en-USAttribution 3.0 United Statesdouble-strand break (DSB)DNA repairbreak-induced replication (BIR)recombinationArticle