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Break-Induced Replication and Genome Stability
Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, USA
* Author to whom correspondence should be addressed.
Received: 10 August 2012; in revised form: 5 October 2012 / Accepted: 8 October 2012 / Published: 16 October 2012
Abstract: Genetic 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.
Keywords: double-strand break (DSB); DNA repair; break-induced replication (BIR); recombination
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Sakofsky, C.J.; Ayyar, S.; Malkova, A. Break-Induced Replication and Genome Stability. Biomolecules 2012, 2, 483-504.
Sakofsky CJ, Ayyar S, Malkova A. Break-Induced Replication and Genome Stability. Biomolecules. 2012; 2(4):483-504.
Sakofsky, Cynthia J.; Ayyar, Sandeep; Malkova, Anna. 2012. "Break-Induced Replication and Genome Stability." Biomolecules 2, no. 4: 483-504.