附近的反向重复序列通过复制模板交换机制融合，产生无着丝粒和双着丝粒的回文染色体。
Nearby inverted repeats fuse to generate acentric and dicentric palindromic chromosomes by a replication template exchange mechanism.
作者信息
Mizuno Ken'Ichi, Lambert Sarah, Baldacci Giuseppe, Murray Johanne M, Carr Antony M
机构信息
Genome Damage and Stability Centre, University of Sussex, Brighton Sussex BN1 9RQ, United Kingdom.
出版信息
Genes Dev. 2009 Dec 15;23(24):2876-86. doi: 10.1101/gad.1863009.
Abstract
Gene amplification plays important roles in the progression of cancer and contributes to acquired drug resistance during treatment. Amplification can initiate via dicentric palindromic chromosome production and subsequent breakage-fusion-bridge cycles. Here we show that, in fission yeast, acentric and dicentric palindromic chromosomes form by homologous recombination protein-dependent fusion of nearby inverted repeats, and that these fusions occur frequently when replication forks arrest within the inverted repeats. Genetic and molecular analyses suggest that these acentric and dicentric palindromic chromosomes arise not by previously described mechanisms, but by a replication template exchange mechanism that does not involve a DNA double-strand break. We thus propose an alternative mechanism for the generation of palindromic chromosomes dependent on replication fork arrest at closely spaced inverted repeats.
摘要
基因扩增在癌症进展中发挥重要作用，并在治疗过程中导致获得性耐药。扩增可通过双着丝粒回文染色体的产生及随后的断裂-融合-桥循环启动。在这里，我们表明，在裂殖酵母中，无着丝粒和双着丝粒回文染色体通过附近反向重复序列的同源重组蛋白依赖性融合形成，并且当复制叉在反向重复序列内停滞时，这些融合频繁发生。遗传和分子分析表明，这些无着丝粒和双着丝粒回文染色体并非通过先前描述的机制产生，而是通过一种不涉及DNA双链断裂的复制模板交换机制产生。因此，我们提出了一种依赖于复制叉在紧密间隔的反向重复序列处停滞而产生回文染色体的替代机制。
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