Trending with Impact: G-Quadruplex Stabilization in Brain Cells

Posted by

Aging (Aging-US)

Aging published this trending research paper on June 19, 2021, entitled, “Differential responses of neurons, astrocytes, and microglia to G-quadruplex stabilization” by researchers from the The University of Texas McGovern Medical School at Houston, TX; Institut de Chimie Moléculaire (ICMUB), UBFC Dijon, CNRS UMR6302, Dijon, France; Rice University, Houston, TX; The University of Texas Graduate School of Biomedical Sciences, Houston, TX. Abstract: The G-quadruplex (G4-DNA or G4) is a secondary DNA structure formed by DNA sequences containing multiple runs of guanines. While it is now firmly established that stabilized G4s lead to enhanced genomic instability in cancer cells, whether and how G4s contribute to genomic instability in brain cells is still not clear. We previously showed that, in cultured primary neurons, small-molecule G4 stabilizers promote formation of DNA double-strand breaks (DSBs) and downregulate the Brca1 gene. Here, we determined if G4-dependent Brca1 downregulation is unique to neurons or if the effects in neurons also occur in astrocytes and microglia. We show that primary neurons, astrocytes and microglia basally exhibit different G4 landscapes. Stabilizing G4-DNA with the G4 ligand pyridostatin (PDS) differentially modifies chromatin structure in these cell types. Intriguingly, PDS promotes DNA DSBs in neurons, astrocytes and microglial cells, but fails to downregulate Brca1 in astrocytes and microglia, indicating differences in DNA damage and repair pathways between brain cell types. Taken together, our findings suggest that stabilized G4-DNA contribute to genomic instability in the brain and may represent a novel senescence pathway in brain aging. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203222 DOI - https://doi.org/10.18632/aging.203222 Full text - https://www.aging-us.com/article/203222/text Correspondence to: Andrey S. Tsvetkov email: andrey.s.tsvetkov@uth.tmc.edu Keywords: G-quadruplex, DNA damage, genomic instability, neurodegeneration, Brca1 About Aging Launched in 2009, Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ or connect with us on: Twitter - https://twitter.com/AgingJrnl​ Facebook - https://www.facebook.com/AgingUS/​ SoundCloud - https://soundcloud.com/aging-us​ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging​ Aging is published by Impact Journals, LLC please visit http://www.ImpactJournals.com​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM