Structural and functional diversity in ATP-dependent nucleosome remodelers
ATP-dependent nucleosome remodeling factors (“remodelers”) use the energy from ATP hydrolysis to non-covalently modify the structure of nucleosomes, the basic unit of DNA packaging in eukaryotic genomes. Remodelers are conserved from yeast to humans, and while they are very diverse in composition--ranging from single-subunit remodelers to multi-subunit complexes of > 1MDa--they all contain a conserved core ATPase that uses DNA translocation to break histone-DNA contacts. Despite this common core, remodelers are capable of producing very different outcomes, from sliding a histone octamer along the DNA, to ejecting histone dimers or octamers, to swapping histone dimers for variant forms.
We are interested in understanding the mechanisms underlying this functional versatility. I will present structural (cryo-EM) and functional data on two different systems: (1) A minimal version of the RSC remodeling complex (a member of the SWI/SNF family of remodelers), which can both slide and eject histone octamers; and (2) CSB, a so-called “orphan” remodeler that plays a role in Transcription-Coupled DNA repair. We recently showed that CSB uses its DNA translocation activity to function as a processivity factor for RNA Polymerase II.
Department of Cellular and Molecular Medicine and Division of Biological Sciences, University of California San Diego La Jolla, CA, USA
Domain 2 - UMR 3215 / U934 - Genetics and Developmental Biology
Hôpital Saint Louis, Paris
CytoMorpho Lab, LPCV / BIG / DRF / CEA