Novel pro- and anti-recombination activities of the Bloom's syndrome helicase
Novel pro- and anti-recombination activities of the Bloom's syndrome helicase
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DOI：
10.1101/gad.1609007
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发表时间：
2007-12-01
影响因子：
10.5
通讯作者：
Mazin, Alexander V.
中科院分区：
文献类型：
--
作者：
Bugreev, Dmitry V.;Yu, Xiong;Mazin, Alexander V.
布卢姆综合征（Bloom's syndrome，BS）是一种常染色体隐性遗传疾病，具有较强的癌症易感性. BS的定义特征是极端的基因组不稳定性。Bloom综合征中突变的基因BLM编码RecQ家族的DNA解旋酶（BLM）。BLM在同源重组中起作用;然而，其确切功能仍有争议。BLM中的突变引起姐妹染色单体和同源染色体之间的过度重组，表明抗重组作用。相反，其他数据表明BLM是重组所必需的。先前表明，体外BLM解旋酶促进重组中间体的破坏、停滞的复制叉的消退和双霍利迪连接的溶解。在这里，我们展示了两个新的活动的BLM：Rad 51-ssDNA（单链DNA）丝，一个活跃的物种，促进同源重组，和刺激的DNA tepair合成中断。利用体外重组反应，我们分析了不同的生化活性的BLM有助于其功能的同源重组。
Bloom's syndrome (BS) is an autosomal recessive disorder characterized by a strong cancer predisposition. The defining feature of BS is extreme genome instability. The gene mutated in Bloom's syndrome, BLM, encodes a DNA helicase (BLM) of the RecQ family. BLM plays a role in homologous recombination; however, its exact function remains controversial. Mutations in the BLM cause hyperrecombination between sister chromatids and homologous chromosomes, indicating an anti-recombination role. Conversely, other data show that BLM is required for recombination. It was previously shown that in vitro BLM helicase promotes disruption of recombination intermediates, regression of stalled replication forks, and dissolution of double Holliday junctions. Here, we demonstrate two novel activities of BLM: disruption of the Rad51-ssDNA (single-stranded DNA) filament, an active species that promotes homologous recombination, and stimulation of DNA tepair synthesis. Using in vitro reconstitution reactions, we analyzed how different biochemical activities of BLM contribute to its functions in homologous recombination.