Abstract
Although homologous recombination is an important pathway for the repair of double-stranded DNA breaks in mitotically dividing eukaryotic cells, these events can also have negative consequences, such as loss of heterozygosity (LOH) of deleterious mutations. We mapped about 140 spontaneous reciprocal crossovers on the right arm of the yeast chromosome IV using single-nucleotide-polymorphism (SNP) microarrays. Our mapping and subsequent experiments demonstrate that inverted repeats of Ty retrotransposable elements are mitotic recombination hotspots. We found that the mitotic recombination maps on the two homologs were substantially different and were unrelated to meiotic recombination maps. Additionally, about 70% of the DNA lesions that result in LOH are likely generated during G1 of the cell cycle and repaired during S or G2. We also show that different genetic elements are associated with reciprocal crossover conversion tracts depending on the cell cycle timing of the initiating DSB.
Highlights
A double-stranded break (DSB) is a potentially lethal DNA lesion that can lead to genomic instability and chromosome rearrangements if not promptly repaired
Double-strand breaks (DSBs) are DNA lesions that can be fatal to a cell if left unrepaired
Yeast cells primarily repair DSBs that are initiated outside of meiosis by mitotic recombination, which can result in physical exchanges between chromosomes, known as crossovers
Summary
A double-stranded break (DSB) is a potentially lethal DNA lesion that can lead to genomic instability and chromosome rearrangements if not promptly repaired. DSBs and other forms of DNA damage (for example, single-stranded nicks or base damage) can result from exogenous (for example, gamma- or UV-radiation) or endogenous sources [1]. Inverted repeats have been called ‘‘at-risk motifs’’ because of their ability to form recombinogenic secondary structures such as hairpins and cruciforms when intrastrand pairing takes place [2]. Hairpin structures can cause replication fork pausing and lead to DSBs [3]. We will show that naturally-occurring inverted repeats act as recombination hotspots in strains with unperturbed DNA replication
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