Journal article
Break induced replication in eukaryotes: mechanisms, functions, and consequences
Critical reviews in biochemistry and molecular biology, Vol.52(4), pp.395-413
07/04/2017
DOI: 10.1080/10409238.2017.1314444
PMCID: PMC6763318
PMID: 28427283
Abstract
Break-induced replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases. This synthesis is drastically different from S-phase replication in that instead of a replication fork, BIR proceeds via a migrating bubble and is associated with conservative inheritance of newly synthesized DNA. This unusual mode of DNA replication is responsible for frequent genetic instabilities associated with BIR, including hyper-mutagenesis, which can lead to the formation of mutation clusters, extensive loss of heterozygosity, chromosomal translocations, copy-number variations and complex genomic rearrangements. In addition to budding yeast experimental systems that were initially employed to investigate eukaryotic BIR, recent studies in different organisms including humans, have provided multiple examples of BIR initiated within different cellular contexts, including collapsed replication fork and telomere maintenance in the absence of telomerase. In addition, significant progress has been made towards understanding microhomology-mediated BIR (MMBIR) that can promote complex chromosomal rearrangements, including those associated with cancer and those leading to a number of neurological disorders in humans.
Details
- Title: Subtitle
- Break induced replication in eukaryotes: mechanisms, functions, and consequences
- Creators
- Cynthia J Sakofsky - Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, US National Institutes of HealthAnna Malkova - Department of Biology, University of Iowa
- Resource Type
- Journal article
- Publication Details
- Critical reviews in biochemistry and molecular biology, Vol.52(4), pp.395-413
- DOI
- 10.1080/10409238.2017.1314444
- PMID
- 28427283
- PMCID
- PMC6763318
- NLM abbreviation
- Crit Rev Biochem Mol Biol
- ISSN
- 1040-9238
- eISSN
- 1549-7798
- Publisher
- Taylor & Francis
- Grant note
- GM084242 / National Institute of General Medical Sciences GM084242 / NIH
- Language
- English
- Date published
- 07/04/2017
- Academic Unit
- Biology
- Record Identifier
- 9984217424102771
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