NMR Investigation of the Interaction between the RecQ C-Terminal Domain of Human Bloom Syndrome Protein and G-Quadruplex DNA from the Human c-Myc Promoter.,Journal of Molecular Biology

当前位置： X-MOL 学术 › J. Mol. Biol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

NMR Investigation of the Interaction between the RecQ C-Terminal Domain of Human Bloom Syndrome Protein and G-Quadruplex DNA from the Human c-Myc Promoter.
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2019-01-10 , DOI: 10.1016/j.jmb.2019.01.010
Sungjin Lee ₁ , Ae-Ree Lee ₂ , Kyoung-Seok Ryu ₃ , Joon-Hwa Lee ₂ , Chin-Ju Park ₁

Affiliation

Bloom syndrome protein (BLM) is one of five human RecQ helicases that participate in DNA metabolism. RecQ C-terminal (RQC) domain is the main DNA binding module of BLM and specifically recognizes G-quadruplex (G4) DNA structures. Because G4 processing by BLM is essential for regulating replication and transcription, both G4 and BLM are considered as potential targets for anticancer therapy. Although several studies have revealed the detailed mechanism of G4 unwinding by BLM, the initial recognition of the G4 structure by the RQC domain is unclear. Here, we investigated the interaction between BLM RQC and the G4 DNA from the c-Myc promoter by NMR spectroscopy. While the signals broadened upon reciprocal titrations, the β-wing of RQC had significant chemical shift perturbations and experienced millisecond timescale dynamics upon G4 binding. A point mutation in the β-wing (N1164A) reduced G4 binding affinity. Our hydrogen-deuterium exchange data indicate that imino protons of G4 were exchanged with deuterium much faster in the presence of RQC. We suggest that RQC binds to G4 by using the β-wing as a separating pin to destabilize the G4. By providing information about the RQC-G4 interaction, our study yields insight into potential strategies for preventing G4 processing by BLM.

中文翻译：

NMR研究人Bloom综合征蛋白的RecQ C末端结构域与人c-Myc启动子的G-四链体DNA之间的相互作用。

Bloom综合征蛋白（BLM）是参与DNA代谢的五种人类RecQ解旋酶之一。RecQ C端（RQC）域是BLM的主要DNA结合模块，可特异性识别G-四链体（G4）DNA结构。由于BLM对G4的加工对于调节复制和转录至关重要，因此G4和BLM均被视为抗癌治疗的潜在靶标。尽管一些研究揭示了BLM展开G4的详细机制，但RQC域对G4结构的初始识别尚不清楚。在这里，我们通过核磁共振波谱研究了BLM RQC和c-Myc启动子的G4 DNA之间的相互作用。双向滴定使信号变宽时，RQC的β翼在结合G4时具有明显的化学位移扰动，并经历了毫秒级的时标动态。β翼（N1164A）中的点突变降低了G4结合亲和力。我们的氢-氘交换数据表明，在存在RQC的情况下，G4的亚氨基质子与氘的交换快得多。我们建议RQC通过使用β翼作为分隔销使G4不稳定来与G4结合。通过提供有关RQC-G4相互作用的信息，我们的研究深入了解了防止BLM处理G4的潜在策略。

更新日期：2019-01-10

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南