The Zuo1 C-terminal domain stabilizes DNA guanosine quadruplex (G4) structures located on chromosome IX in Saccharomyces cerevisiae

Ines Burkhart, Michaela Limmer, J. Carlos Penedo , Li-Chia Sauer, Harald Schwalbe*, Katrin Paeschke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Deoxyguanosine quadruplexes (G4s) form stable non-B-DNA structures that can affect transcription, replication, and genome stability. Depending on various factors including cation binding, G4s can fold into different topologies, which can be linked to distinct function. In cells, G4 folding, function, and unfolding is affected by proteins that specifically target G4s. Zuo1 is a G4-binding protein in yeast. To investigate Zuo1 binding and its consequences on G4 formation and topology, we characterized Zuo1’s interaction with G4s, both in vitro and in vivo. The C-terminus (Zuo1348-433) of Zuo1 interacts with the G4s. We characterized this interaction by combining nuclear magnetic resonance spectroscopy, single-molecule Förster Resonance Energy Transfer (smFRET), and in vivo experiments with G4IX that is located on yeast chromosome IX. The Zuo1–G4IX interaction stabilizes this G4 structure and triggers conformational shifts depending on the cation environment. The data presented here demonstrate that Zuo1 targets a specific conformation state of G4 IX, modulates G4 toppology.
Original languageEnglish
Article numbergkaf1055
Number of pages15
JournalNucleic Acids Research
Volume53
Issue number20
Early online date3 Nov 2025
DOIs
Publication statusPublished - 11 Nov 2025

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