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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chromatin Assembly and Disassembly
  • DNA Helicases / metabolism*
  • DNA Repair
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Nucleosomes / metabolism*
  • Poly (ADP-Ribose) Polymerase-1 / metabolism*

Substances

  • DNA-Binding Proteins
  • Nucleosomes
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • DNA Helicases
  • CHD1L protein, human