Stabilization of G-quadruplex DNA structures in Schizosaccharomyces pombe causes single-strand DNA lesions and impedes DNA replication
Journal article, 2020

G-quadruplex (G4) structures are stable non-canonical DNA structures that are implicated in the regulation of many cellular pathways. We show here that the G4-stabilizing compound PhenDC3 causes growth defects in Schizosaccharomyces pombe cells, especially during S-phase in synchronized cultures. By visualizing individual DNA molecules, we observed shorter DNA fragments of newly replicated DNA in the PhenDC3-treated cells, suggesting that PhenDC3 impedes replication fork progression. Furthermore, a novel single DNA molecule damage assay revealed increased single-strand DNA lesions in the PhenDC3-treated cells. Moreover, chromatin immunoprecipitation showed enrichment of the leading-strand DNA polymerase at sites of predicted G4 structures, suggesting that these structures impede DNA replication. We tested a subset of these sites and showed that they form G4 structures, that they stall DNA synthesis in vitro and that they can be resolved by the breast cancer-associated Pif1 family helicases. Our results thus suggest that G4 structures occur in S. pombe and that stabilized/unresolved G4 structures are obstacles for the replication machinery. The increased levels of DNA damage might further highlight the association of the human Pif1 helicase with familial breast cancer and the onset of other human diseases connected to unresolved G4 structures.


Ikenna Obi

Umeå University

Matilda Rentoft

Umeå University

Vandana Singh

Chalmers, Biology and Biological Engineering, Chemical Biology

Jan Jamroskovic

Umeå University

Karam Chand

Umeå University

E. Chorell

Umeå University

Fredrik Westerlund

Chalmers, Biology and Biological Engineering, Chemical Biology

Nasim Sabouri

Umeå University

Nucleic Acids Research

0305-1048 (ISSN) 1362-4962 (eISSN)

Vol. 48 19 10998-11015

Subject Categories

Biochemistry and Molecular Biology

Other Basic Medicine

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Areas of Advance

Health Engineering





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