Abstract Completion of DNA replication before chromosome segregation is essential for the stable maintenance of the genome. Under replication stress, DNA synthesis may persist beyond S phase, especially in genomic regions that are difficult to proceed with the replication processes. Incomplete replication in mitosis emerges as non‐disjoined segment in mitotic chromosomes leading to anaphase bridges. The resulting chromosome rearrangements are not well characterized, however. Here, we report that incomplete replication due to SMC5/6 deficiency impairs sister chromatid disjunction at difficult‐to‐replicate regions, including common fragile sites. These non‐disjoined regions manifest as cytologically defined symmetric gaps, causing anaphase bridges. These bridges break at the gaps, leading to telomere loss, micronucleation, and fragmentation. Subsequently, fusions between telomere‐deficient chromosomes generate complex chromosomal rearrangements, including dicentric chromosomes, suggesting the occurrence of breakage‐fusion‐bridge cycle. Additionally, chromosomes in micronuclei were pulverized, indicative of chromothripsis. Our findings suggest that incomplete replication facilitates complex chromosomal rearrangements, which may contribute to genomic instability in human cancers.

Yoshiharu Kusano

Yasuha Kinugasa

Satoshi Tashiro

Toru Hirota

Genes to Cells

GENES TO CELLS 为发表描述分子和细胞生物学重要方面的论文提供了一个国际论坛。该杂志旨在发表在相关领域提供概念性进展的论文。将特别强调旨在了解生物学事件的基本机制的工作。

Genes to Cells is an international forum dedicated to publishing important research papers in the field of molecular and cellular biology. The journal aims to present conceptual advancements in related areas, with a particular emphasis on studies that seek to understand the fundamental mechanisms underlying biological events.

《Genes to Cells》是一个国际论坛，专注于发表分子和细胞生物学领域的重要研究论文。该杂志旨在发布在相关领域内提供概念性进展的研究成果，特别强调揭示生物学事件基本机制的研究工作。

Category	Quartile
生物学	4
生物学, 细胞生物学	4
生物学, 遗传学	4

Chromosomal rearrangements associated with SMC5/6 deficiency in DNA replication

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Journal Info

Category	Quartile
GENETICS & HEREDITY	4