Venue: Seminar Hall
Speaker : Dr. Raushan Kumar Singh, University of Massachusetts Medical School, Worcester (USA)
Title : SWR1C: A nucleosome editing machine
Dr. Raushan Kumar Singh. Currently is working as Postdoctoral Associate, University of Massachusetts Medical School, Worcester (USA). Prior to this, Dr. Singh has worked Graduate Research Assistant (Biochemistry) in North Dakota State University, Fargo, USA for more than five years. Hereceived M.S. in Animal Biotechnology from National Dairy Research Institute, Karnal, India and obtained PhD degree from North Dakota State University, Fargo, USA.
Abstract: The SWR1C chromatin remodeling enzyme catalyzes an ATP-dependent replacement/editing of nucleosomal H2A with the H2A.Z variant, regulating key DNA-mediated processes, such as transcription, DNA replication and repair. This talk will be focused on the latest findings of our biophysical/kinetic investigation of the histone exchange reaction employing ensemble FRET, fluorescence correlation spectroscopy (FCS), and the transient kinetics of SWR1C ATPase motor (machine). Our studies indicate that SWR1C modulates nucleosome dynamics on both the millisecond and microsecond timescales, poising the nucleosome for the dimer exchange reaction. The transient kinetic analysis of the remodeling reaction under single turnover conditions unraveled a striking asymmetry in the ATP-dependent replacement of nucleosomal dimers, promoted by localized DNA translocation. Furthermore, the kinetic analysis of SWR1C ATPase motor shows that the chemo-mechanical coupling in the remodeling enzyme is notably similar to that of the acto-myosin ATPase. Taken together, our transient kinetic studies unravel new intermediates and provide seminal insights into the SWR1C-catalyzed dimer exchange reaction, as well as shedding light on how the mechanics of H2A.Z deposition might contribute to transcriptional regulation in vivo.
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