Journal article
Break-Induced Replication and Genome Stability
Biomolecules (Basel, Switzerland), Vol.2(4), pp.483-504
2012
DOI: 10.3390/biom2040483
PMCID: PMC3678771
PMID: 23767011
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.
Details
- Title: Subtitle
- Break-Induced Replication and Genome Stability
- Creators
- Cynthia J Sakofsky - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, USA; Email: (C.J.S.); (S.A.)Sandeep Ayyar - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, USA; Email: (C.J.S.); (S.A.)Anna Malkova - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202, USA; Email: (C.J.S.); (S.A.)
- Resource Type
- Journal article
- Publication Details
- Biomolecules (Basel, Switzerland), Vol.2(4), pp.483-504
- DOI
- 10.3390/biom2040483
- PMID
- 23767011
- PMCID
- PMC3678771
- NLM abbreviation
- Biomolecules
- ISSN
- 2218-273X
- eISSN
- 2218-273X
- Publisher
- MDPI
- Language
- English
- Date published
- 2012
- Academic Unit
- Biology
- Record Identifier
- 9984217424602771
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