Sequencing of micronuclear DNAs

Chromosome missegregation into a micronucleus can provoke complex and localized genomic rearrangements known as chromothripsis, but the underlying mechanisms are not established. Here we find that mitotic errors generate structural rearrangements on initially missegregated chromosomes through a two-step mechanism of micronucleus-mediated DNA fragmentation in mitosis coupled to NHEJ-dependent reassembly in the subsequent cell cycle.

染色体错误分离进入微核（micronucleus）可引发被称为染色体碎裂（chromothripsis）的复杂局域性基因组重排，但其潜在机制尚未阐明。本研究发现，有丝分裂错误可通过两步作用机制，在初始发生错误分离的染色体上诱发结构重排：即有丝分裂阶段由微核介导的DNA片段化，与后续细胞周期中依赖非同源末端连接（NHEJ）的染色体重组装过程相偶联。