Rogers Cody M, Wang Joseph Che-Yen, Noguchi Hiroki, Imasaki Tsuyoshi, Takagi Yuichiro, Bochman Matthew L
Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN 47405, USA.
Electron Microscopy Center, Indiana University, Bloomington, IN 47405, USA.
Nucleic Acids Res. 2017 May 19;45(9):5217-5230. doi: 10.1093/nar/gkx151.
The five human RecQ helicases participate in multiple processes required to maintain genome integrity. Of these, the disease-linked RecQ4 is the least studied because it poses many technical challenges. We previously demonstrated that the yeast Hrq1 helicase displays similar functions to RecQ4 in vivo, and here, we report the biochemical and structural characterization of these enzymes. In vitro, Hrq1 and RecQ4 are DNA-stimulated ATPases and robust helicases. Further, these activities were sensitive to DNA sequence and structure, with the helicases preferentially unwinding D-loops. Consistent with their roles at telomeres, telomeric repeat sequence DNA also stimulated binding and unwinding by these enzymes. Finally, electron microscopy revealed that Hrq1 and RecQ4 share similar structural features. These results solidify Hrq1 as a true RecQ4 homolog and position it as the premier model to determine how RecQ4 mutations lead to genomic instability and disease.
五种人类RecQ解旋酶参与维持基因组完整性所需的多个过程。其中，与疾病相关的RecQ4研究最少，因为它带来了许多技术挑战。我们之前证明酵母Hrq1解旋酶在体内表现出与RecQ4相似的功能，在此，我们报告这些酶的生化和结构特征。在体外，Hrq1和RecQ4是DNA刺激的ATP酶和强大的解旋酶。此外，这些活性对DNA序列和结构敏感，解旋酶优先解开D环。与它们在端粒中的作用一致，端粒重复序列DNA也刺激这些酶的结合和解旋。最后，电子显微镜显示Hrq1和RecQ4具有相似的结构特征。这些结果巩固了Hrq1作为真正的RecQ4同源物的地位，并将其定位为确定RecQ4突变如何导致基因组不稳定和疾病的首要模型。
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