Bloom Syndrome Helicase Stimulates RAD51 DNA Strand Exchange Activity through a Novel Mechanism
Bloom Syndrome Helicase Stimulates RAD51 DNA Strand Exchange Activity through a Novel Mechanism
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DOI：
10.1074/jbc.m109.029371
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发表时间：
2009-09-25
影响因子：
4.8
通讯作者：
Mazin, Alexander V.
中科院分区：
文献类型：
--
作者：
Bugreev, Dmitry V.;Mazina, Olga M.;Mazin, Alexander V.
BLM是RecQ家族的一种解旋酶，其缺失或失活会导致Bloom综合征，这是一种具有强烈癌症倾向的遗传性疾病。虽然BLM的确切功能仍然未知，但遗传数据表明BLM参与了基因重组和DNA修复过程。以前，我们证明了BLM可以破坏促进同源重组初始步骤的RAD 51-单链DNA丝。然而，这种破坏仅在RAD 51以无活性ADP结合形式存在时发生。在这里，我们调查的BLM与活性ATP结合形式的RAD 51-单链DNA丝的相互作用。令人惊讶的是，我们发现BLM刺激RAD 51的DNA链交换活性。与BLM的解旋酶活性相反，这种刺激不需要ATP水解。这些数据表明一种新的BLM功能，即刺激RAD 51 DNA配对。我们的研究结果表明，在刺激DNA配对的BLM的RAD 51核蛋白丝构象的重要作用。
Loss or inactivation of BLM, a helicase of the RecQ family, causes Bloom syndrome, a genetic disorder with a strong predisposition to cancer. Although the precise function of BLM remains unknown, genetic data has implicated BLM in the process of genetic recombination and DNA repair. Previously, we demonstrated that BLM can disrupt the RAD51-single-stranded DNA filament that promotes the initial steps of homologous recombination. However, this disruption occurs only if RAD51 is present in an inactive ADP-bound form. Here, we investigate interactions of BLM with the active ATP-bound form of the RAD51-single-stranded DNA filament. Surprisingly, we found that BLM stimulates DNA strand exchange activity of RAD51. In contrast to the helicase activity of BLM, this stimulation does not require ATP hydrolysis. These data suggest a novel BLM function that is stimulation of the RAD51 DNA pairing. Our results demonstrate the important role of the RAD51 nucleoprotein filament conformation in stimulation of DNA pairing by BLM.