The present invention provides methods of negatively modulating the Werner protein (WRN) to inhibit proliferative cells characterized by high microsatellite instability (MSI-H), for example to treat proliferative diseases (such as cancer) characterized by high MSI (MSI-H). Further provided are compositions used in such methods.

The present invention provides methods of negatively modulating the Werner protein (WRN) to inhibit proliferative cells characterized by high microsatellite instability (MSI-H), for example to treat proliferative diseases (such as cancer) characterized by high MSI (MSI-H). Further provided are compositions used in such methods.

The present invention provides that exosomes from ovarian cancer patients contain nuclear proteins and genomic DNA at an increased proportion. As such, detecting nuclear-derived exosomes provides a method of early detection of ovarian cancer. Furthermore, the level of nuclear-derived exosomes can be monitored over time to assess responsiveness to genotoxic therapy.

The present invention provides assays and methods for studying DNA topology and topoisomerases. The assays and methods utilize a circular plasmid DNA comprising one or more hairpin structures and the ability of T5 exonuclease (T5E) to digest the circular plasmid DNA in a specific configuration. The assays and methods can be used as a high throughput screening for inhibitors of, for example, DNA gyrases and DNA topoisomerases I for anticancer drug and antibiotics discovery.

The present invention provides assays and methods for studying DNA topology and topoisomerases. The assays and methods utilize a circular plasmid DNA comprising one or more hairpin structures and the ability of T5 exonuclease (T5E) to digest the circular plasmid DNA in a specific configuration. The assays and methods can be used as a high throughput screening for inhibitors of, for example, DNA gyrases and DNA topoisomerases I for anticancer drug and antibiotics discovery.

The present invention provides assays and methods for studying DNA topology and topoisomerases. The assays and methods utilize a circular plasmid DNA comprising one or more hairpin structures and the ability of T5 exonuclease (T5E) to digest the circular plasmid DNA in a specific configuration. The assays and methods can be used as a high throughput screening for inhibitors of, for example, DNA gyrases and DNA topoisomerases I for anticancer drug and antibiotics discovery.

The present invention provides assays and methods for studying DNA topology and topoisomerases. The assays and methods utilize a circular plasmid DNA comprising one or more hairpin structures and the ability of T5 exonuclease (T5E) to digest the circular plasmid DNA in a specific configuration. The assays and methods can be used as a high throughput screening for inhibitors of, for example, DNA gyrases and DNA topoisomerases I for anticancer drug and antibiotics discovery.

Methods for assaying function and/or activity and/or potency of isomerohydrolase proteins are provided.

Aspects of the disclosure relate to compositions of enzyme-binding polypeptides (EBPs) that modify the substrate specificity of an enzyme and a method for identifying an EBP that modifies substrate specificity of an enzyme binding at least one substrate, the method comprising: contacting the enzyme with a polypeptide library comprising a plurality of EBPs that bind different epitopes of the enzyme; identifying EBPs that bind to the enzyme to form an EBP-enzyme complex; assaying for the activity level and substrate specificity of the EBP-enzyme complex; and identifying EBPs that modify the substrate specificity of the enzyme by identifying EBPs that, when in an EBP-enzyme complex, have a different substrate specificity than un-complexed EBP; wherein the catalytic rate constant of the EBP-enzyme complex is ≥50% of the un-complexed enzyme for at least one substrate and/or wherein the EBP-enzyme complex retains binding to a substrate.

Aspects of the disclosure relate to compositions of enzyme-binding polypeptides (EBPs) that modify the substrate specificity of an enzyme and a method for identifying an EBP that modifies substrate specificity of an enzyme binding at least one substrate, the method comprising: contacting the enzyme with a polypeptide library comprising a plurality of EBPs that bind different epitopes of the enzyme; identifying EBPs that bind to the enzyme to form an EBP-enzyme complex; assaying for the activity level and substrate specificity of the EBP-enzyme complex; and identifying EBPs that modify the substrate specificity of the enzyme by identifying EBPs that, when in an EBP-enzyme complex, have a different substrate specificity than un-complexed EBP; wherein the catalytic rate constant of the EBP-enzyme complex is ≥50% of the un-complexed enzyme for at least one substrate and/or wherein the EBP-enzyme complex retains binding to a substrate.