Journal article
Stressed? Break-induced replication comes to the rescue
DNA repair, Vol.142, 103759
10/2024
DOI: 10.1016/j.dnarep.2024.103759
PMCID: PMC12970614
PMID: 39241677
Abstract
Break-induced replication (BIR) is a homologous recombination (HR) pathway that repairs one-ended DNA double-strand breaks (DSBs), which can result from replication fork collapse, telomere erosion, and other events. Eukaryotic BIR has been mainly investigated in yeast, where it is initiated by invasion of the broken DNA end into a homologous sequence, followed by extensive replication synthesis proceeding to the chromosome end. Multiple recent studies have described BIR in mammalian cells, the properties of which show many similarities to yeast BIR. While HR is considered as “error-free” mechanism, BIR is highly mutagenic and frequently leads to chromosomal rearrangements—genetic instabilities known to promote human disease. In addition, it is now recognized that BIR is highly stimulated by replication stress (RS), including RS constantly present in cancer cells, implicating BIR as a contributor to cancer genesis and progression. Here, we discuss the past and current findings related to the mechanism of BIR, the association of BIR with replication stress, and the destabilizing effects of BIR on the eukaryotic genome. Finally, we consider the potential for exploiting the BIR machinery to develop anti-cancer therapeutics.
•BIR is driven by a migrating bubble with the conservative inheritance of new DNA.•BIR often leads to mutations, chromosome rearrangements, and loss of heterozygosity.•BIR in yeast and humans shares multiple genetic similarities.•Eukaryotes are reluctant to use BIR for repair of collapsed replication forks.•Under replication stress, BIR is readily employed to handle replication fork collapse.
Details
- Title: Subtitle
- Stressed? Break-induced replication comes to the rescue
- Creators
- Rosemary S. Lee - Department of Biochemistry & Structural Biology, University of Texas Health San Antonio, San Antonio, TX 78229, USAJerzy M. Twarowski - University of IowaAnna Malkova - Department of Biochemistry & Structural Biology, University of Texas Health San Antonio, San Antonio, TX 78229, USA
- Resource Type
- Journal article
- Publication Details
- DNA repair, Vol.142, 103759
- DOI
- 10.1016/j.dnarep.2024.103759
- PMID
- 39241677
- PMCID
- PMC12970614
- NLM abbreviation
- DNA Repair (Amst)
- ISSN
- 1568-7864
- eISSN
- 1568-7856
- Publisher
- Elsevier B.V
- Grant note
- National Institute of General Med-ical Sciences: R35GM127006
This work was supported by the National Institute of General Med-ical Sciences grant R35GM127006 to AM.
- Language
- English
- Date published
- 10/2024
- Academic Unit
- Biology
- Record Identifier
- 9984701857602771
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