G‑Quadruplex Helicase DHX36/G4R1 Engages Nuclear Lamina Proteins in Quiescent Breast Cancer Cells

• Published in: ACS omega Vol. 5; no. 38; pp. 24916 - 24926
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: American Chemical Society 29.09.2020
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.0c03723

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.