DNA Synthesis Generates Terminal Duplications That Seal End-to-End Chromosome Fusions
DNA Synthesis Generates Terminal Duplications That Seal End-to-End Chromosome Fusions
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DOI：
10.1126/science.1199022
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发表时间：
2011-04-22
期刊：
影响因子：
56.9
通讯作者：
Ahmed, Shawn
中科院分区：
文献类型：
--
作者：
Lowden, Mia Rochelle;Flibotte, Stephane;Ahmed, Shawn
端粒酶缺乏的情况下发生的端到端染色体融合可引发基因组复制。70多年来，这些重复仅仅被归因于断裂-融合桥循环。为了验证这一假设，我们检查了从秀丽隐杆线虫端粒复制突变体中分离的端到端融合体。基因组水平的重排显示融合的染色体末端有中断的末端复制伴随着模板转换事件。这些特征与人类基因组间质段与疾病相关的重复非常相似。先前提出了一种称为叉速和模板切换的模型来解释这种重复，即发生大的、不连续的基因组片段的混杂复制。因此，基于DNA合成的过程可以在没有断裂-融合桥循环的情况下，创造出密封端到端融合的复制。
End-to-end chromosome fusions that occur in the context of telomerase deficiency can trigger genomic duplications. For more than 70 years, these duplications have been attributed solely to breakage-fusion-bridge cycles. To test this hypothesis, we examined end-to-end fusions isolated from Caenorhabditis elegans telomere replication mutants. Genome-level rearrangements revealed fused chromosome ends having interrupted terminal duplications accompanied by template-switching events. These features are very similar to disease-associated duplications of interstitial segments of the human genome. A model termed Fork Stalling and Template Switching has been proposed previously to explain such duplications, where promiscuous replication of large, noncontiguous segments of the genome occurs. Thus, a DNA synthesis-based process may create duplications that seal end-to-end fusions, in the absence of breakage-fusion-bridge cycles.