Abstract

G-quadruplex (G4) structures are highly stable four-stranded DNA and RNA secondary structures held together by non-canonical guanine base pairs. G4 sequence motifs are enriched at specific sites in eukaryotic genomes, suggesting regulatory functions of G4 structures during different biological processes. Considering the high thermodynamic stability of G4 structures, various proteins are necessary for G4 structure formation and unwinding. In a yeast one-hybrid screen, we identified Slx9 as a novel G4-binding protein. We confirmed that Slx9 binds to G4 DNA structures in vitro. Despite these findings, Slx9 binds only insignificantly to G-rich/G4 regions in Saccharomyces cerevisiae as demonstrated by genome-wide ChIP-seq analysis. However, Slx9 binding to G4s is significantly increased in the absence of Sgs1, a RecQ helicase that regulates G4 structures. Different genetic and molecular analyses allowed us to propose a model in which Slx9 recognizes and protects stabilized G4 structures in vivo.

Highlights

  • The observation that secondary structures within DNA or RNA can influence biological processes had a great impact on modern biology

  • An interaction of a protein with the G4 motif from chromosome IX (G4IX) motif resulted in the expression of the AUR-1C gene and, growth on aureobasidin A medium

  • Different in vitro and in vivo experiments in various organisms demonstrated the regulatory potential of G4 structures, and highlight the challenges that such a structure poses for the cell [2,8,20,21,26]

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Summary

Introduction

The observation that secondary structures within DNA or RNA can influence biological processes had a great impact on modern biology (reviewed in [1,2,3,4]). G4 structures are discussed as being a regulatory tool in the cell for telomere maintenance, transcription, translation, and even origin activation [7,10,11,12,13]. This assumption is further supported by computational and in vitro and in vivo experiments. These data demonstrated that G4 structures form at specific sites (e.g., promoters) and regulate a specific pathway (e.g., transcription) [6,10,14,15,16,17,18]

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