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.

不正确的DNA双链断裂（DSB）修复会导致许多癌症和人类各种先天性疾病的复杂基因组重排（CGR）。三核苷酸重复序列，如（GAA）_ñ重复在弗里德赖希共济失调，（CTG）_ñ在肌强直性营养不良重复序列，和（CGG）_ñ易碎X综合征中的重复序列，在重复道内也会发生双链断裂，然后进行DNA修复。绘制CGR的结果图对于理解其原因和潜在的表型效应很重要。但是，CGR的高分辨率制图历来是一项费力且高技能的过程。长读DNA测序技术（特别是Nanopore测序）的最新进展已使以单碱基对分辨率快速鉴定CGR成为可能。在这里，我们已使用全基因组纳米孔测序来表征几种CGR，这些CGR源自酿酒酵母（GAA）_n微卫星中天然存在的DSB 。这些数据使我们对导致CGR的DSB修复机制有了重要的认识。