Multiple roles for PARP1 in ALC1-dependent nucleosome remodeling

Soon Keat Ooi, Shigeo Sato, Chieri Tomomori-Sato, Ying Zhang, Zhihui Wen, Charles A.S. Banks, Michael P. Washburn, Jay R. Unruh, Laurence Florens, Ronald C. Conaway, Joan W. Conaway

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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(ADPribose) 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.

Original languageEnglish (US)
Article numbere2107277118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number36
DOIs
StatePublished - Sep 7 2021
Externally publishedYes

Keywords

  • CHD1L
  • Nucleosome binding
  • Nucleosome remodeling
  • Poly(ADP-ribose) synthesis
  • SNF2 family ATPase

ASJC Scopus subject areas

  • General

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