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

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.