Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA
| Autor: | Nayun Kim, Christopher R. Lopez, Shashank Hambarde, Kevin D. Raney, Jun Gao, Wezley C. Griffin, Yang Yu, Shubeena Chib, Grzegorz Ira, Shivani Singh |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genome instability Saccharomyces cerevisiae Proteins HMG-box Transcription Genetic Base pair Saccharomyces cerevisiae Biology Genome Integrity Repair and Replication Genomic Instability 03 medical and health sciences Gene Expression Regulation Fungal Genetics Humans Amino Acid Sequence DNA Fungal Replication protein A DNA clamp Binding Sites Genome 030102 biochemistry & molecular biology Sequence Homology Amino Acid DNA Helicases DNA binding site DNA-Binding Proteins G-Quadruplexes 030104 developmental biology DNA Topoisomerases Type I DNA supercoil Sequence Alignment In vitro recombination Protein Binding Transcription Factors |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| Popis: | G-quadruplex or G4 DNA is a non-B secondary DNA structure consisting of a stacked array of guanine-quartets that can disrupt critical cellular functions such as replication and transcription. When sequences that can adopt Non-B structures including G4 DNA are located within actively transcribed genes, the reshaping of DNA topology necessary for transcription process stimulates secondary structure-formation thereby amplifying the potential for genome instability. Using a reporter assay designed to study G4-induced recombination in the context of an actively transcribed locus in Saccharomyces cerevisiae, we tested whether co-transcriptional activator Sub1, recently identified as a G4-binding factor, contributes to genome maintenance at G4-forming sequences. Our data indicate that, upon Sub1-disruption, genome instability linked to co-transcriptionally formed G4 DNA in Top1-deficient cells is significantly augmented and that its highly conserved DNA binding domain or the human homolog PC4 is sufficient to suppress G4-associated genome instability. We also show that Sub1 interacts specifically with co-transcriptionally formed G4 DNA in vivo and that yeast cells become highly sensitivity to G4-stabilizing chemical ligands by the loss of Sub1. Finally, we demonstrate the physical and genetic interaction of Sub1 with the G4-resolving helicase Pif1, suggesting a possible mechanism by which Sub1 suppresses instability at G4 DNA. |
| Databáze: | OpenAIRE |
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