The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants
The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants
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DOI：
10.1073/pnas.1431624100
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发表时间：
2003-07-08
影响因子：
11.1
通讯作者：
Campbell, JL
中科院分区：
文献类型：
--
作者：
Imamura, O;Campbell, JL
布卢姆综合征是一种深刻的和早期的癌症易感性的疾病，在这种疾病中，细胞变得超可变，表现出高频率的姐妹染色单体交换，并表现出微核增加。BLM是布鲁姆综合征中突变的基因，此前已被克隆，BLM蛋白是DNA解旋酶RecQ家族的一员。许多证据表明，BLM直接参与DNA复制或DNA复制过程中的监视，但其具体作用尚不清楚。本研究表明，hBLM可以抑制酵母DNA复制突变体dna2-1的温度敏感性生长缺陷和DNA损伤敏感性。dna2-1突变体在解旋酶核酸酶中存在缺陷，该酶在Okazaki片段成熟过程中需要与关键的酿酒酵母（Saccharomyces cerevisiae, sc） FEN1核酸酶协调，或者在scFEN1活性受损时补偿scFEN1。通过酵母提取物的共免疫沉淀，我们发现人类BLM与scDna2和scFEN1相互作用，表明人类BLM与scFEN1和scDna2参与相同的DNA复制或修复步骤。
Bloom syndrome is a disorder of profound and early cancer predisposition in which cells become hypermutable, exhibit high frequency of sister chromatid exchanges, and show increased micronuclei. BLM, the gene mutated in Bloom syndrome, has been cloned previously, and the BLM protein is a member of the RecQ family of DNA helicases. Many lines of evidence suggest that BLM is involved either directly in DNA replication or in surveillance during DNA replication, but its specific roles remain unknown. Here we show that hBLM can suppress both the temperature-sensitive growth defect and the DNA damage sensitivity of the yeast DNA replication mutant dna2-1. The dna2-1 mutant is defective in a helicase-nuclease that is required either to coordinate with the crucial Saccharomyces cerevisiae (sc) FEN1 nuclease in Okazaki fragment maturation or to compensate for scFEN1 when its activity is impaired. We show that human BLM interacts with both scDna2 and scFEN1 by using coimmunoprecipitation from yeast extracts, suggesting that human BLM participates in the same steps of DNA replication or repair as scFEN1 and scDna2.