Nanopore sequencing of complex genomic rearrangements in yeast reveals mechanisms of repeat-mediated double-strand break repair
Abstract
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 employed whole-genome Nanopore sequencing to characterize several CGRs that originated from naturally occurring DSBs at (GAA)n microsatellites in S. cerevisiae. These data gave us important insights into the mechanisms of DSB repair leading to CGRs.
- Received July 21, 2017.
- Accepted October 26, 2017.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International license), as described at http://creativecommons.org/licenses/by-nc/4.0/.
