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SWR1C: A nucleosome editing machine

December 7 @ 4:00 pm - 5:00 pm

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.Discipline/Coordinating Entity: Biological Engineering

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Date:
December 7
Time:
4:00 pm - 5:00 pm
Event Category: