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JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Nanopore sequencing of complex genomic rearrangements in yeast reveals mechanisms of repeat-mediated double-strand break repair.
Genome Research 2017 December
Improper DNA double-strand break (DSB) repair results in complex genomic rearrangements (CGRs) in many cancers and various congenital disorders in humans. Trinucleotide repeat sequences, such as (GAA)n repeats in Friedreich's ataxia, (CTG)n repeats in myotonic dystrophy, and (CGG)n repeats in fragile X syndrome, are also subject to double-strand breaks within the repetitive tract followed by DNA repair. Mapping the outcomes of CGRs is important for understanding their causes and potential phenotypic effects. However, high-resolution mapping of CGRs has traditionally been a laborious and highly skilled process. Recent advances in long-read DNA sequencing technologies, specifically Nanopore sequencing, have made possible the rapid identification of CGRs with single base pair resolution. Here, we have used whole-genome Nanopore sequencing to characterize several CGRs that originated from naturally occurring DSBs at (GAA)n microsatellites in Saccharomyces cerevisiae These data gave us important insights into the mechanisms of DSB repair leading to CGRs.
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