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Title [sv]
Den fyrsträngade DNA strukturens roll i hälsa och sjukdom
Title [en]
G-quadruplex DNA structures- in health and disease
Abstract [en]
DNA can form stable secondary structures such as the G-quadruplex (G4), a four-stranded DNA structure. G4 structures are associated to human diseases, but they are also emerging as novel targets for cancer therapeutics. Sequences with the potential to form G4 structures (G4 motifs) are not randomly distributed in the genome, but their locations are evolutionary conserved and found in essentially all genomes. However, their functions are poorly understood.Here, we propose both in vivo and in vitro approaches to understand the functions of G4 structures in vivo, and how we can target them in cancer therapeutics. We aim to determine the effects of novel G4-stabilizing compounds that we discovered in a high-throughput screen and to examine their potential to target cancer cells. Our hypothesis is that binding of G4-stabilizing compounds to G4 structures arrests DNA replication, causes DNA damage, and leads to cell death.First, we will examine both the in vitro and in vivo effects of these novel G4-stabilizing compounds, as well as analogs of these compounds. Next, we will determine which DNA repair pathways that are affected, and the types of cancer cells these compounds are more effective against. Finally, we will use the best compounds to determine the functions of G4 structures in vivo. Our ultimate goal is to identify novel anti-cancer drugs that are more selective than current drugs.
Principal InvestigatorSabouri, Nasim
Coordinating organisation
Umeå University
Funder
Period
2019-01-01 - 2021-12-31
National Category
Biochemistry and Molecular BiologyCell and Molecular Biology
Identifiers
DiVA, id: project:1547Project, id: 2018-02651_VR

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