The mechanism of ATP-dependent nucleosome remodeling -- Dissection of the function of important protein domains and nucleosomal epitopes

• Applicant: Professor Dr. Felix Müller-Planitz
• Subject Area: Biochemistry
• Term: from 2014 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258481232

Nucleosome remodeling enzymes reposition nucleosomes along DNA in all eukaryotic cells. They thereby render the DNA that is protected by the nucleosome accessible to other factors. Nucleosome remodeling affects fundamental genetic processes that rely on accessibility of DNA, such as transcription, replication, recombination and DNA repair. It is therefore not surprising that several remodeling enzymes have been implicated in human diseases. All remodeling enzymes contain an ATPase 'motor' domain that can autonomously reposition nucleosomes. Other, accessory protein domains evolved to regulate this motor module and steer the reaction towards different outcomes. Understanding this regulation on the molecular level holds the key to uncover the overall remodeling mechanism. In our work program we plan to dissect an intricate regulatory network imparted by specific remodeler domains in conjunction with nucleosomal epitopes. Quantitative biochemical and biophysical methods and innovative structural approaches will be employed. We hope to obtain insight into the inner workings of these fascinating molecular machines, and we may discover principles that are applicable to more complex remodeling enzymes.

• DFG Programme: Research Grants