Ribosomal DNA G-quadruplex (rDNA G4)

Ribosomal DNA G-quadruplexes (rDNA G4s) are non-canonical secondary structures formed within the guanine-rich sequences of the ribosomal DNA repeats located in the nucleolus. These structures play a pivotal role in regulating ribosomal RNA (rRNA) transcription by modulating the activity of RNA polymerase I (Pol I) and the binding of nucleolar proteins like nucleolin (Nucleic Acids Research, 2019). In many cancers, ribosome biogenesis is hyperactivated to meet the high protein synthesis demands of rapidly dividing cells, making rDNA G4s an attractive therapeutic target (Nature Reviews Cancer, 2018). Small molecule stabilizers, such as CX-5461 and Quarfloxin, bind to these G4 structures to disrupt Pol I transcription, thereby inducing nucleolar stress and activating DNA damage response pathways (Cancer Discovery, 2017). This targeted disruption leads to cell cycle arrest and apoptosis, particularly in cancer cells that are "addicted" to high levels of ribosome production (Nature Chemical Biology, 2008). Consequently, rDNA G4s represent a strategic vulnerability in oncology, providing a mechanism to selectively inhibit the fundamental process of protein synthesis in malignant tissues (Trends in Pharmacological Sciences, 2020).

Other names

rDNA G-quadruplexNucleolar G-quadruplexRibosomal DNA G4rDNA G-quadruplex DNA

Stabilization of G-quadruplex structures within the ribosomal DNA template, which physically blocks the progression of RNA polymerase I, leading to the inhibition of ribosomal RNA synthesis and the induction of nucleolar stress-mediated apoptosis.