GSE123707 Genome wide binding of Top2 (in WT and uls1 delta cells) and Uls1 (in WT cells) both in the presence and absence of the Top2 poison acriflavine (ACF)

Contributor : Helder FerreiraSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Saccharomyces cerevisiaeTopoisomerase II (Top2) is an essential enzyme that decatenates DNA via a transient Top2-DNA covalent intermediate. This intermediate can be stabilised by a class of drugs termed Top2 poisons, resulting in massive DNA damage. Thus, Top2 activity is a double-edged sword that needs to be carefully controlled to maintain genome stability. We show that Uls1, an ATP-dependent chromatin remodelling (Snf2) enzyme, can alter Top2 chromatin binding and prevent Top2 poisoning in yeast. Deletion mutants of ULS1 are hypersensitive to the Top2 poison acriflavine (ACF), activating the DNA damage checkpoint. We map Uls1 ’s Top2 interaction domain and show that this, together with its ATPase activity, is essential for Uls1 function. By performing ChIP-seq, we show that ACF leads to a general increase in Top2 binding across the genome. We map Uls1 binding sites and identify tRNA genes as key regions where Uls1 asso ciates after ACF treatment. Importantly, the presence of Uls1 at these sites prevents ACF-dependent Top2 accumulation. Our data reveal the effect of Top2 poisons on the global Top2 binding landscape and highlights the role of Uls1 in antagonising Top2 function. Remodelling Top2 binding is thus an im portant new means by which Snf2 enzymes promote genome stability.

Source: GEO: Gene Expression Omnibus - April 17, 2019 Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Saccharomyces cerevisiae Source Type: research