G-quadruplexes at play: DNA changes, chromatin deposition, and gene transcription

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    Abstract

    In addition to the classical double helix structure, DNA can also take on other forms. An example is the G-quadruplex (G4). A G4 looks a bit like a mini-apartment building and can form from a single guanine-rich DNA strand. Despite posing an obstacle during the replication of DNA molecules, sequences with the potential to form G4s are present in many key regions of our genomes, suggesting G4s may be of functional importance.
    Hence, our research has focused on the genome-wide relationship between G4s and various processes in the cell. We evaluated the potential role of G4s in gene expression regulation in cells of patients with Bloom Syndrome, a rare disease caused by absence of the BLM enzyme. BLM can resolve G4s, but our results indicate that BLM's interaction with the ribosomal DNA locus may be of much greater importance to healthy cells. Furthermore, we investigated how G4s affect the distribution of the “packaging” proteins that help to organize the DNA strands. Using our newly developed technique called double-click-seq, we show that the deposition of the packaging proteins onto replicated DNA is a non-random process that clearly deviates at G4 sites. Lastly, we have explored how the sequences of human G4s mutate over time.
    Together, our findings contribute to a better understanding of the cellular effects of genome-wide G4 stabilization. In doing so, we hope to advance the development of future medical treatments as new studies focus on using G4s as a therapeutic target in cancer treatment strategies.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Guryev, Victor, Supervisor
    • Lansdorp, Peter, Supervisor
    • Colomé Tatché, Maria, Co-supervisor
    Award date27-Nov-2023
    Place of Publication[Groningen]
    Publisher
    DOIs
    Publication statusPublished - 2023

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