Cancer predisposition caused by elevated mitotic recombination in Bloom mice
Cancer predisposition caused by elevated mitotic recombination in Bloom mice
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DOI：
10.1038/82548
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发表时间：
2000-12-01
期刊：
影响因子：
30.8
通讯作者：
Bradley, A
中科院分区：
文献类型：
--
作者：
Luo, GB;Santoro, IM;Bradley, A
布卢姆综合征是一种与基因组不稳定相关的疾病，导致受影响的人容易患癌症。Bloom细胞系显示增加的姐妹染色单体交换，但精通各种DNA损伤的修复。这种疾病的根本原因是编码RECQ DNA解旋酶的基因突变。使用胚胎干细胞技术，我们已经产生了可行的布卢姆小鼠，容易患各种癌症。这些小鼠的细胞系显示有丝分裂重组率升高。我们证明，有丝分裂重组导致的体内杂合性丢失（洛）率增加构成了这些小鼠肿瘤易感性的潜在机制。
Bloom syndrome is a disorder associated with genomic instability that causes affected people to be prone to cancer. Bloom cell lines show increased sister chromatid exchange, yet are proficient in the repair of various DNA lesions. The underlying cause of this disease are mutations in a gene encoding a RECQ DNA helicase. Using embryonic stem cell technology, we have generated viable Bloom mice that are prone to a wide variety of cancers. Cell lines from these mice show elevations in the rates of mitotic recombination. We demonstrate that the increased rate of loss of heterozygosity (LOH) resulting from mitotic recombination in vivo constitutes the underlying mechanism causing tumour susceptibility in these mice.