Richardson Adam E, Zentz Zachary A, Chambers Antonio E, Sandwith Siara N, Reisinger Michael A, Saunders Destinee W, Tompkins Joshua D, Riggs Arthur D, Routh Eric D, Rubenstein Eric M, Smaldino Melissa A, Vaughn James P, Haney Robert A, Smaldino Philip J
Department of Biology, Ball State University, Muncie, Indiana 47306, United States.
Department of Diabetes Complications and Metabolism, City of Hope, Duarte, California 91010, United States.
ACS Omega. 2020 Sep 16;5(38):24916-24926. doi: 10.1021/acsomega.0c03723. eCollection 2020 Sep 29.
G-quadruplexes (G4s) are nucleic acid structures found enriched within gene regulatory sequences. G4s control fundamental cellular processes, including replication, transcription, and translation. Proto-oncogenes are enriched with G4 sequences, while tumor-suppressor genes are depleted, suggesting roles for G4s in cell survival and proliferation. Specialized helicases participate in G4-mediated gene regulation via enzymatic unwinding activity. One such enzyme, DHX36/G4R1, is the major G4-helicase and is a master regulator of G4-DNAs and mRNAs. G4-resolution promotes the expression of proproliferative genes; as such, DHX36/G4R1 promotes cell proliferation. Little is known about how DHX36/G4R1 itself is regulated in nondividing cells. We hypothesized that DHX36/G4R1 protein binding partners are altered when a cell transitions from a dividing to a quiescent state. We found that DHX36/G4R1 co-purifies with a distinct set of proteins under quiescent conditions, which may represent a novel complex that regulates DHX36/G4R1 during cell cycle transitions and have implications for development and cancer.
G-四链体（G4s）是在基因调控序列中富集的核酸结构。G4s控制着包括复制、转录和翻译在内的基本细胞过程。原癌基因富含G4序列，而肿瘤抑制基因则缺乏，这表明G4s在细胞存活和增殖中发挥作用。专门的解旋酶通过酶促解旋活性参与G4介导的基因调控。一种这样的酶，DHX36/G4R1，是主要的G4解旋酶，是G4-DNA和mRNA的主要调节因子。G4的解旋促进了促增殖基因的表达；因此，DHX36/G4R1促进细胞增殖。关于DHX36/G4R1本身在非分裂细胞中如何被调控知之甚少。我们假设当细胞从分裂状态转变为静止状态时，DHX36/G4R1的蛋白质结合伙伴会发生改变。我们发现，在静止条件下，DHX36/G4R1与一组不同的蛋白质共同纯化，这可能代表一种新型复合物，在细胞周期转变过程中调节DHX36/G4R1，对发育和癌症具有重要意义。
