Nanopore sequencing of complex genomic rearrangements in yeast reveals mechanisms of repeat-mediated double-strand break repair.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • McGinty, RJ; Rubinstein, RG; Neil, AJ; Dominska, M; Kiktev, D; Petes, TD; Mirkin, SM

Published Date

  • December 2017

Published In

Volume / Issue

  • 27 / 12

Start / End Page

  • 2072 - 2082

PubMed ID

  • 29113982

Pubmed Central ID

  • PMC5741057

Electronic International Standard Serial Number (EISSN)

  • 1549-5469

Digital Object Identifier (DOI)

  • 10.1101/gr.228148.117


  • eng

Conference Location

  • United States