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Updated: Jun 9, 2025

Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
G-quadruplex DNA and RNA in cellular senescence
Rocio Diaz Escarcega1, Paul Marshall2, Andrey S Tsvetkov1,3,4
1Department of Neurology, University of Texas McGovern Medical School, Houston, TX, United States.
Abstract:
Normal cells divide, are damaged, and are repaired across their lifetime. As cells age, they enter cellular senescence, characterized by a permanent state of cell-cycle arrest triggered by various stressors. The molecular mechanisms that regulate senescent phenotypes have been actively investigated over the last several decades; however, one area that has been neglected is how G-quadruplex (G4) DNA and RNA (G4-DNA and G4-RNA) mediate senescence. These non-canonical four-stranded DNA and RNA structures regulate most normative DNA and RNA-dependent processes, such as transcription, replication, and translation, as well as pathogenic mechanisms, including genomic instability and abnormal stress granule function. This review also highlights the contribution of G4s to sex differences in age-associated diseases and emphasizes potential translational approaches to target senescence and anti-aging mechanisms through G4 manipulation.
Insights
Cellular senescence, a key aging process, is influenced by G-quadruplex (G4) DNA and RNA structures. Targeting G4s offers potential for anti-aging therapies and understanding sex differences in age-related diseases.
Area of Science:
- Molecular Biology
- Genetics
- Aging Research
Background:
- Cellular senescence is a permanent cell-cycle arrest state linked to aging.
- Molecular mechanisms of senescence are widely studied, but the role of G-quadruplexes (G4s) is under-explored.
- G4 structures in DNA and RNA regulate fundamental cellular processes.
Purpose of the Study:
- To review the role of G-quadruplex (G4) DNA and RNA in mediating cellular senescence.
- To highlight G4 contributions to sex differences in age-associated diseases.
- To explore G4 manipulation for anti-aging strategies.
Main Methods:
- Literature review of studies on G-quadruplexes and cellular senescence.
- Analysis of G4 roles in transcription, replication, translation, and genomic stability.
- Examination of G4 involvement in age-related diseases and sex differences.
Main Results:
- G4 structures are implicated in regulating senescent phenotypes.
- G4s influence key cellular processes and can contribute to genomic instability.
- G4s play a role in sex-specific aging phenotypes and diseases.
Conclusions:
- G-quadruplexes are significant regulators of cellular senescence.
- Targeting G4 structures presents a promising avenue for anti-aging interventions.
- Understanding G4s can elucidate sex differences in aging and disease.
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