Zuo1 supports G4 structure formation and directs repair towards nucleotide excision repair

Nucleic acids can fold into G-quadruplex (G4) structures that can fine tune biological processes. Proteins are required to recognize G4 structures and coordinate their function. We identify Zuo1 as a novel G4-binding protein in a yeast one-hybrid screen. Biochemical and molecular experiments in yeast confirm that Zuo1 specifically binds to G4 structures in vitro and in vivo. In vivo in the absence of Zuo1 less G4 structures form, cell growth slows and cells become UV sensitive. Subsequent experiments reveal that these cellular changes are due to reduced levels of G4 structures. Interestingly, Zuo1 function and binding to G4 structures results in the recruitment of nucleotide excision repair (NER) factors, which has a positive effect on genome stability. Cells lacking functional NER as well as Zuo1 accumulate G4s structures, which become accessible for translesion synthesis. Our results suggest a model in which Zuo1 supports NER function and regulates the choice of the DNA repair pathway near G4 structures. Overall design: Examination of the Zuo1 binding sites in the yeast chromatin