2. Academic Validation
  3. Multiple roles for PARP1 in ALC1-dependent nucleosome remodeling

Multiple roles for PARP1 in ALC1-dependent nucleosome remodeling

  • Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2107277118. doi: 10.1073/pnas.2107277118.
Soon-Keat Ooi 1,  Shigeo Sato 1,  Chieri Tomomori-Sato 1,  Ying Zhang 1,  Zhihui Wen 1,  Charles A S Banks 1,  Michael P Washburn 1 2,  Jay R Unruh 1,  Laurence Florens 1,  Ronald C Conaway 1 3,  Joan W Conaway 4 3
Affiliations

Affiliations

  • 1 Stowers Institute for Medical Research, Kansas City, MO 64110.
  • 2 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160.
  • 3 Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160.
  • 4 Stowers Institute for Medical Research, Kansas City, MO 64110; Joan.Conaway@UTSouthwestern.edu.
PMID: 34465625 DOI: 10.1073/pnas.2107277118
Abstract

The SNF2 family ATPase Amplified in Liver Cancer 1 (ALC1) is the only chromatin remodeling Enzyme with a poly(ADP-ribose) (PAR) binding macrodomain. ALC1 functions together with poly(ADP-ribose) polymerase PARP1 to remodel nucleosomes. Activation of ALC1 cryptic ATPase activity and the subsequent nucleosome remodeling requires binding of its macrodomain to PAR chains synthesized by PARP1 and NAD+ A key question is whether PARP1 has a role(s) in ALC1-dependent nucleosome remodeling beyond simply synthesizing the PAR chains needed to activate the ALC1 ATPase. Here, we identify PARP1 separation-of-function mutants that activate ALC1 ATPase but do not support nucleosome remodeling by ALC1. Investigation of these mutants has revealed multiple functions for PARP1 in ALC1-dependent nucleosome remodeling and provides insights into its multifaceted role in chromatin remodeling.

Keywords

CHD1L; SNF2 family ATPase; nucleosome binding; nucleosome remodeling; poly(ADP-ribose) synthesis.

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