Hamza Balci, Kent State University, A Single Molecule Approach to Study Protein, Small Molecule, and G-Quadruplex

Date: Mon. February 20th, 2017, 12:45 pm-1:45 pm
Location: Rockefeller 221 (Miller Room)
Website: https://www.kent.edu/physics/profile/hamza-balci

A Single Molecule Approach to Study Protein, Small Molecule, and  G-Quadruplex Interactions

Hamza Balci

Kent State University, Physics Department, Kent, OH

 

G-quadruplex (GQ) structures are non-canonical nucleic acid secondary structures that form in guanine-rich segments of the genome, most prominently at telomeres. In addition, several hundred thousand potential GQ forming sequences have been identified in human genome, with particularly higher frequency at promoter regions. When GQ structures (GQs) form at telomeres, they cap chromosome ends and are involved in stabilizing these vulnerable regions. Also, GQs have been shown to regulate transcription and translation level gene expression when they form in promoter regions of DNA and 5′-UTR of RNA, respectively. However, GQs are typically thermally more stable than double stranded DNA formed by Watson-Crick pairing and need to be unfolded during DNA replication and repair for effective progression of these processes. A number of single stranded DNA (ssDNA) binding proteins and helicases are specialized in unfolding these structures. Understanding the structural and kinetic aspects protein-mediated GQ unfolding is one of main themes of this presentation. In particular, our studies on the role of GQ and its synergistic cooperation with members of shelterin complex in protecting telomeres will be presented. In addition, our work on RecQ family of helicases and how they interact with GQ will be presented. Two members of this family, RECQ5 and BLM, show significantly different efficiency in destabilizing GQ structures. Such variations have implications on the role of GQs in several syndromes associated with defects in RecQ helicases. Finally, our recent work on GQ stabilizing small molecules will be presented. Such small molecules have considerable potential as anti-cancer drugs as they hinder telomerase activity and interfere with DNA replication and repair. Our single molecule studies on the binding kinetics of a telomestatin derivative while interacting with GQ will be presented